Transferrin receptor antibodies

ABSTRACT

Isolated and purified antiserum or antibody specific for an immunogenic material is provided. Such immunogenic material may comprise purified and isolated transferrin receptor protein of a strain of Haemophilus or a fragment or an analog of the transferrin receptor protein, recombinant Tbp1 or Tbp2 proteins and isolated and purified Tbp1 and Tbp2 proteins, and synthetic peptides.

REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No. 08/337,483 filed Nov. 8, 1995, which itself is a continuation-in-part of U.S. patent application Ser. No. 08/175116, filed Dec. 29, 1993 (now abandoned), which itself is a continuation-in-part of U.S. patent application Ser. No. 08/148,968 filed Nov. 8, 1993 (now abandoned).

FIELD OF INVENTION

The present invention is related to the molecular cloning of genes encoding transferrin receptor and in particular to the cloning of transferrin receptor genes from Haemophilus influenzae.

BACKGROUND OF THE INVENTION

Encapsulated Haemophilus influenzae type b strains are the major cause of bacterial meningitis and other invasive infections in young children. However, the non-encapsulated or non-typable H. influenzae (NTHi) are responsible for a wide range of human diseases including otitis media, epiglottitis, pneumonia, and tracheobronchitis. Vaccines based upon H. influenzae type b capsular polysaccharide conjugated to diphtheria toxoid (Berkowitz et al., 1987. Throughout this application, various references are referred to in parenthesis to more fully describe the state of the art to which this invention pertains. Full bibliographic information for each citation is found at the end of the specification, immediately preceding the claims. The disclosures of these references are hereby incorporated by reference into the present disclosure), tetanus toxoid (Classon et al., 1989 and U.S. Pat. No. 4,496,538), or Neisseria meningitidis outer membrane protein (Black et al., 1991) have been effective in reducing H. influenzae type b-induced meningitis, but not NTHi-induced disease (Bluestone, 1982).

Otitis media is the most common illness of early childhood with 60-70% of all children of less than 2 years of age experiencing between one and three ear infections. Chronic otitis media is responsible for hearing, speech and cognitive impairments in children. H. influenzae infections account for about 30% of the cases of acute otitis media and about 60% of chronic otitis media. In the United States alone, treatment of otitis media costs between 1 and 2 billion dollars per year for antibiotics and surgical procedures such as tonsillectomies, adenoidectomies and insertion of tympanostomy tubes. Furthermore, many of the causative organisms of otitis media are becoming resistant to antibiotic treatment. An effective prophylactic vaccine against otitis media is thus desirable. Non-typable strains of H. influenzae are also important pathogens responsible for pneumonia in the elderly and other individuals who are particularly susceptible to respiratory infections. There is thus a need for antigens from H. influenzae which are useful as components in immunogenic preparations that provide protection against the many serotypes of H. influenzae.

Iron is an essential nutrient for the growth of many bacteria. Several human pathogens, such as H. influenzae, Branhamella catarrhalis, N. meningitidis, N. gonorrhoeae and non-pathogenic commensal Neisseria strains, can utilize human transferrin as an iron source (Schryvers, 1988; Schryvers and Lee, 1989; Mickelsen and Sparling, 1981). The bacterial transferrin receptor (TfR) is composed of two chains, Tbp1 and Tbp2. In strains of H. influenzae, the molecular weight of Tbp1 is approximately 100,000, whereas the molecular weight of Tbp2 is variable, ranging from 60,000 to 90,000, depending upon the strain (Schryvers and Gray-Owen, 1992; Holland et al., 1992). Expression of H. influenzae transferrin receptor is thought to be iron-and/or hemin-regulated (Morton et al., 1993) and a putative fur-binding site (Braun and Hantke, 1991) has been identified upstream of tbp2. This sequence is found in the promoter region of genes which are negatively regulated by iron, including N. meningitidis TfR (Legrain et al., 1993). The promoter is followed by the tbp2 and tbpl genes, an arrangement found in other bacterial TfR operons (Legrain et al, 1993; Wilton et al., 1993). Antibodies which block the access of the transferrin receptor to its iron source may prevent bacterial growth. In addition, antibodies against TfR that are opsonizing or bactericidal may also provide protection by alternative mechanisms. Thus, the transferrin receptor, fragments thereof, its constituent chains, or peptides derived therefrom are vaccine candidates to protect against H. influenzae disease. Mice immunized with N. meningitidis TfR proteins in Freund's adjuvant were protected from homologous challenge and the anti-TfR antisera were bactericidal and protective in a passive transfer assay (Danve et al., 1993). Pigs immunized with recombinant A. pleuropneumoniae Tbp2 were protected against homologous challenge but not heterologous challenge (Rossi-Campos et al., 1992). These data indicate the efficacy of TfR-based vaccines in protection from disease. It would be desirable to provide the sequence of the DNA molecule that encodes transferrin receptor and peptides corresponding to portions of the transferrin receptor and vectors containing such sequences for diagnosis, immunization and the generation of diagnostic and immunological reagents.

Poliovirus is an enterovirus, a genus of the family Picornaviridae. There are three distinct serotypes of the virus, and multiple strains within each serotype. Virulent strains are causative agents of paralytic poliomyelitis. Attenuated strains, which have reduced potential to cause paralytic disease, and inactivated virulent strains, are used as vaccines. Infection with the virus induces long-lasting, protective, mucosal immunity. Inoculation with inactivated poliovirus vaccines can also induce a mucosal immune response.

The structure of poliovirus is known, and is highly conserved among strains and serotypes. The structures of several other picornaviruses (viruses belonging to genera of the family Picornaviridae) have also been determined, and have been shown to be closely related to the structure of poliovirus. It is possible to express foreign epitopes on the capsid of polioviruses (Murdin et al, 1992) and this work has been extended to other picornaviruses. Epitopes which have been expressed are usually short, well defined, contiguous epitopes, and most have been expressed within poliovirus neutralisation antigenic site I (NAgI) or the equivalent site on other picornaviruses. This site includes the loop linking beta strands B and C (the BC loop) of poliovirus capsid protein VP1. The BC loop of VP1 is a surface-exposed loop of nine amino acids which can be replaced and extended with at least twenty-five heterologous amino acids (Murdin et al, 1991). Hybrid or chimeric polioviruses expressing transferrin receptor epitopes, which grow to a high titer and are immunogenic, would be useful as vaccines and as tools for the generation of immunological reagents.

SUMMARY OF THE INVENTION

The present invention is directed towards the provision of purified and isolated nucleic acid molecules encoding a transferrin receptor of a strain of Haemophilus or a fragment or an analog of the transferrin receptor protein. The nucleic acid molecules provided herein are useful for the specific detection of strains of Haemophilus, and for diagnosis of infection by Haemophilus. The purified and isolated nucleic acid molecules provided herein, such as DNA, are also useful for expressing the TfR genes by recombinant DNA means for providing, in an economical manner, purified and isolated transferrin receptor subunits, fragments or analogs thereof. The transferrin receptor, subunits or fragments thereof or analogs thereof, as well as nucleic acid molecules encoding the same and vectors containing such nucleic acid molecules, are useful in immunogenic compositions against diseases caused by Haemophilus, the diagnosis of infection by Haemophilus and as tools for the generation of immunological reagents. Monoclonal antibodies or mono-specific antisera (antibodies) raised against the transferrin receptor protein produced in accordance with aspects of the present invention are useful for the diagnosis of infection by Haemophilus, the specific detection of Haemophilus (in for example in vitro and in vivo assays) and for the treatment of diseases caused by Haemophilus.

Peptides corresponding to portions of the transferrin receptor or analogs thereof are useful immunogenic compositions against disease caused by Haemophilus, the diagnosis of infection by Haemophilus and as tools for the generation of immunological reagents. Monoclonal antibodies or antisera raised against these peptides, produced in accordance with aspects of the present invention, are useful for the diagnosis of infection by Haemophilus, the specific detection of Haemophilus (in, for example, in vitro and in vivo assays) and for use in passive immunization as a treatment of disease caused by Haemophilus.

In accordance with one aspect of the present invention, there is provided a purified and isolated nucleic acid molecule encoding a transferrin receptor protein of a strain of Haemophilus, more particularly, a strain of H. influenzae, specifically a strain of H. influenzae type b, such as H. influenzae type b strain DL63, Eagan or MinnA, or a non-typable strain of H. influenzae, such as H. influenzae strain PAK 12085, SB33, SB12, SB29, SB30 or SB32, or a fragment or an analog of the transferrin receptor protein.

In one preferred embodiment of the invention, the nucleic acid molecule may encode only the Tbp1 protein of the Haemophilus strain or only the Tbp2 protein of the Haemophilus strain. In another preferred embodiment of the invention, the nucleic acid may encode a fragment of the transferrin receptor protein of a strain of Haemophilus having a conserved amino acid sequence which is conserved among bacteria that produce transferrin receptor protein. Such conserved amino acid sequence may have an amino acid sequence contained within the amino acid sequence of the peptides shown in Tables 2 and 3 below for Haemophilus influenzae type b strain Eagan as well as corresponding peptides of other strains of Haemophilus influenzae.

In another aspect of the present invention, there is provided a purified and isolated nucleic acid molecule having a DNA sequence selected from the group consisting of (a) any one of the DNA sequences set out in FIGS. 3, 4, 5, 6, 7, 8, 9, 10 or 11 (SEQ ID NOS: 1, 2, 3, 4, 105, 108, 110, 112, 114) or the complementary DNA sequence of any one of said sequences; (b) a DNA sequence encoding one of the amino acid sequences set out in FIGS. 3, 4, 5, 6, 7, 8, 9, 10 or 11 (SEQ ID NOS: 5, 6, 7, 8, 9, 10, 11, 12, 106, 107, 109, 111, 113, 115) or the complementary DNA sequence thereto; and (c) a DNA sequence which hybridizes under stringent conditions to any one of the DNA sequences defined in (a) or (b). The DNA sequence defined in (c) preferably has at least about 90% sequence identity with any one of the DNA sequences defined in (a) and (b).

In an additional aspect, the present invention includes a vector adapted for transformation of a host, comprising a nucleic acid molecule as provided herein. The vector may be one having the characteristics of plasmid DS-712-1-3 having ATCC accession number 75603 or plasmid JB-1042-7-6 having ATCC accession number 75607.

The plasmids may be adapted for expression of the encoded transferrin receptor, fragments or analogs thereof, in a heterologous or homologous host, in either a lipidated or non-lipidated form. Accordingly, a further aspect of the present invention provides an expression vector adapted for transformation of a host comprising a nucleic acid molecule as provided herein and expression means operatively coupled to the nucleic acid molecule for expression by the host of the transferrin receptor protein or the fragment or analog of the transferrin receptor protein. In specific embodiments of this aspect of the invention, the nucleic acid molecule may encode substantially all the transferrin receptor protein, only the Tbp1 protein or only the Tbp2 protein of the Haemophilus strain. The expression means may include a nucleic acid portion encoding a leader sequence for secretion from the host of the transferrin receptor protein or the fragment or the analog of the transferrin receptor protein. The expression means also may include a nucleic acid portion encoding a lipidation signal for expression from the host of a lipidated form of the transferrin receptor protein or the fragment or the analog of the transferrin receptor protein. The expression plasmid may have the identifying characteristics of plasmid JB-1468-29, JB-1600-1 or JB-1424-2-8. The host may be selected from, for example, Escherichia coli, Bacillus, Haemophilus, fungi, yeast or baculovirus and Semliki Forest virus expression systems may be used.

In an additional aspect of the invention, there is provided a transformed host containing an expression vector as provided herein. Such host may selected from JB-1476-2-1, JB-1437-4-1 and JB-1607-1-1. The invention further includes a recombinant transferrin receptor protein or fragment or analog thereof producible by the transformed host.

As described in more detail below, there has been produced Tbp1 and Tbp2 protein receptors separate from each other. Further aspects of the present invention, therefore, provide an isolated and purified Tbp1 protein of a strain of Haemophilus free from the Tbp2 protein of the Haemophilus strain and an isolated and purified Tbp2 protein of a strain of Haemophilus free from the Tbp1 protein of the Haemophilus strain. The Haemophilus strain may be H. influenzae type b or a non-typable strain of H. influenzae.

The present invention further provides synthetic peptides corresponding to portions of the transferrin receptor. Accordingly, in a further aspect of the invention, there is provided a synthetic peptide having no less than six amino acids and no more than 150 amino acids and containing an amino acid sequence corresponding to a portion only of a transferrin receptor protein of a strain of bacteria or of an analog the transferrin receptor protein. The bacterial strain preferably is a Haemophilus strain, particularly a H. influenzae strain, specifically a strain of H. influenzae type b or a non-typable strain of H. influenzae.

The peptides provided herein may comprise an amino acid sequence which is conserved among bacteria that produces transferrin receptor protein, including strains of Haemophilus. The peptide may include an amino acid sequence LEGGFYGP (SEQ ID NO: 74) or LEGGFYG (SEQ ID NO: 85). The peptides provided herein may have an amino acid sequence selected from those presented in Table 2 or 3 below for the Eagan strain of H. influenzae type b and corresponding amino acid sequences for other strains of H. influenzae.

In accordance with another aspect of the invention, an immunogenic composition is provided which comprises at least one active component selected from at least one nucleic acid molecule as provided herein, at least one recombinant protein as provided herein, at least one of the purified and isolated Tbp1 or Tbp2 proteins, as provided herein, at least one synthetic peptide, as provided herein, and a live vector, as provided herein, and a pharmaceutically acceptable carrier thereof or or vector therefor. The at least one active component produces an immune response when administered to a host.

The immunogenic compositions provided herein may be formulated as a vaccine for in vivo administration to protect against diseases caused by bacterial pathogens that produce transferrin receptors. For such purpose, the compositions may be formulated as a microparticle, capsule or liposome preparation. Alternatively, the compositions may be provided in combination with a targeting molecule for delivery to specific cells of the immune system or to mucosal surfaces. The immunogenic composition may comprise a plurality of active components to provide protection against disease caused by a plurality of species of transferrin receptor producing bacteria. The immunogenic compositions may further comprise an adjuvant.

In accordance with another aspect of the invention, there is provided a method for inducing protection against infection or disease caused by Haemophilus or other bacteria that produce transferrin receptor protein, comprising the step of administering to a susceptible host, such as a human, an effective amount of the immunogenic composition as recited above.

In accordance with another aspect of the invention, an antiserum or antibody specific for the recombinant protein, the isolated and purified Tbp1 protein or Tbp2 protein, synthetic peptide or the immunogenic composition, is provided.

In a further aspect, there is provided a live vector for delivery of transferrin receptor to a host, comprising a vector containing the nucleic acid molecule as described above. The vector may be selected from Salmonella, BCG, adenovirus, poxvirus, vaccinia and poliovirus. The vector may specifically be poliovirus and the nucleic acid molecule may code for a fragment of transferrin receptor having an amino acid sequence of LEGGFYGP (SEQ ID NO: 74) or LEGGFYG (SEQ ID NO: 85). The present invention further includes a plasmid vector having the identifying characteristics of pT7TBP2A, pT7TBP2B, pT7TBP2C or pT7TBP2D (ATCC designation Nos. 75931, 75932, 75933, 75934).

An additional aspect of the invention provides a strain of Haemophilus that does not produce transferrin receptor protein. Such strain may comprise a gene encoding transferrin receptor which is functionally disabled, such as by insertional mutagenesis. The Haemophilus strain may be one that has been attenuated and the attenuated strain may comprise the vector for delivery of transferrin receptor.

As mentioned above, one aspect of the invention provides novel Tbp1 or Tbp2 protein of a strain of Haemophilus, preferably a strain of Haemophilus influenzae, which is isolated and purified and free from the other. A yet further aspect of the present invention provides a method for producing such proteins. Accordingly, in this yet further aspect, the present invention provides a method of producing an isolated and purified Tbp1 or Tbp2 protein of a strain of Haemophilus, comprising the steps of (a) providing a recombinant host expressing, in inclusion bodies, Tbp1 or Tbp2 protein, but not both; (b) growing the host to provide a cell mass; (c) disrupting the cell mass to provide a cell lysate; (d) fractionating the cell lysate to provide a first supernatant and a first pellet, the first supernatant comprising substantially a large proportion of soluble host proteins; (e) separating the first supernatant from the first pellet; (f) selectively extracting the first pellet to remove substantially all soluble host proteins and host membrane proteins therefrom to provide a second supernatant and an extracted pellet containing the inclusion bodies; (g) separating the second supernatant from the extracted pellet; (h) solubilizing the extracted pellet to provide a solubilized extract; and (i) fractionating the solubilized extract to provide a Tbp1 or Tbp2 protein containing fraction.

The cell lysate may be fractionated to provide the first supernatant and first pellet may be effected by at least one detergent extraction.

The solubilized extract may be fractionated by gel filtration to provide the Tbp1 or Tbp2 protein containing fraction, which may be subsequently dialyzed to remove at least the detergent and provide a further purified solution of Tbp1 or Tbp2 protein.

BRIEF DESCRIPTION OF DRAWINGS

The present invention will be further understood from the following description with reference to the drawings, in which:

FIG. 1A shows the restriction map of two plasmid clones (pBHT1 and pBHT2) of the transferrin receptor operon of Haemophilus influenzae type b strain DL63.

FIG. 1B shows the restriction map of clones S-4368-3-3 and JB-901-5-3 containing TfR genes from H. influenzae type b strain Eagan.

FIG. 1C shows the restriction map of clone DS-712-1-3 containing the transferrin receptor gene from H. influenzae type b strain MinnA.

FIG. 1D shows the restriction map of clone JB-1042-7-6 containing the transferrin receptor gene from the non-typable H. influenzae strain PAK 12085.

FIG. 2 illustrates the organization and restriction maps of the cloned Tbp1 and Tbp2 genes of identified strains and the genetic organization of the TfR operon with two genes (tbp1 and tbp2) in tandem forming an operon under the transcriptional regulation of a single promoter and also depicts the 3.0 kb DNA fragment of pBHIT2 used to probe libraries for TfR genes from the Haemophilus strains.

FIG. 3 shows the nucleotide sequences of the transferrin receptor genes (SEQ ID NO: 1) and their deduced amino acid sequences (SEQ ID NO: 5 - Tbp1 and SEQ ID NO: 6 - Tbp2) from H. influenzae type b, strain DL63. The underlined amino acid sequences correspond to peptides of Tbp1 identified by amino acid sequencing. The putative signal sequences are indicated by double overlining and correspond to residues 1 to 17 for Tbp1 and 1 to 25 for Tbp2.

FIG. 4 shows the nucleotide sequences of the transferrin receptor genes (SEQ ID NO: 2) and their deduced amino acid sequences (SEQ ID NO: 7 - Tbp1 and SEQ ID NO: 8 - Tbp2) from H. influenzae type b strain Eagan. Putative -35, -10 and ribosomal binding site sequences are overlined.

FIG. 5 shows the nucleotide sequences of the transferrin receptor genes (SEQ ID NO: 3) and their deduced amino acid sequences (SEQ ID NO: 9 - Tbp1 and SEQ ID NO: 10 - Tbp2) from H. influenzae type b strain MinnA. Putative -35, -10 and ribosomal binding site sequences are overlined.

FIG. 6 shows the nucleotide sequences of the transferrin receptor genes (SEQ ID NO: 4) and their deduced amino acid sequences (SEQ ID NO. 11 - Tbp1 and SEQ ID NO. 12 - Tbp2) from the non-typable H. influenzae strain PAK 12085. Putative -35, -10 and ribosomal binding site sequences are overlined.

FIG. 7 shows the nucleotide sequences of the transferrin receptor genes (SEQ ID NO: 105) and their deduced amino acid sequences (SEQ ID NO. 106 -Tbp1 and SEQ ID NO. 107 - Tbp2) from the non-typable H. influenzae strain SB33.

FIG. 8 shows the nucleotide sequence of the Tbp2 gene (SEQ ID NO: 108) and the deduced amino acid sequence (SEQ ID NO: 109 - Tbp2) from non-typable strain H. influenzae strain SB12.

FIG. 9 shows the nucleotide sequence of the Tbp2 gene (SEQ ID NO: 110) and the deduced amino acid sequence (SEQ ID NO: 111 - Tbp2) from non-typable strain H. influenzae strain SB29.

FIG. 10 shows the nucleotide sequence of the Tbp2 gene (SEQ ID NO: 112) and the deduced amino acid sequence (SEQ ID NO: 113 - Tbp2) from non-typable strain H. influenzae strain SB30.

FIG. 11 shows the nucleotide sequence of the Tbp2 gene (SEQ ID NO: 114) and the deduced amino acid sequence (SEQ ID NO: 115 - Tbp2) from non-typable strain H. influenzae strain SB32.

FIG. 12A shows the nucleotide sequences of the promoter regions and 5'-end of the tbp2 genes from H. influenzae strains Eagan (SEQ ID NO: 116), MinnA (SEQ ID NO: 117), PAK 12085 (SEQ ID NO: 118) and SB33 (SEQ ID NO: 119). The coding strand primer used to amplify tbp2 genes by PCR is underlined (SEQ ID NO: 120).

FIG. 12B shows the nucleotide sequence of the intergenic region and 5'-end of the tbpl genes from H. influenzae strains Eagan (SEQ ID NO: 121), MinnA (SEQ ID NO: 122), DL63 (SEQ ID NO: 123), PAK 12085 (SEQ ID NO: 124), SB12 (SEQ ID NO: 125), SB29 (SEQ ID NO: 126), SB30 (SEQ ID NO: 127), and SB32 (SEQ ID NO: 128). The non-coding strand primer used to amplify the tbp2 genes by PCR is underlined (SEQ ID NO: 129).

FIG. 13 shows the agarose gel analysis of PCR amplified thp2 genes from non-typable H. influenzae strains SB12, SB29, SB30, SB32 and SB33. Lane 1 is SB33, lane 2 is SB12, lane 3 is SB29, lane 4 is SB30, lane 5 is SB32.

FIG. 14 shows a comparison of the amino acid sequences of Tbp1 from H. influenzae strains Eagan, DL63, PAK 12085 and SB33 (SEQ ID NOS: 7, 5, 11 and 106), N. meningitidis strains B16B6 and M982 (SEQ ID NOS: 94 and 95), and N. gonorrhoeae strain FA19 (SEQ ID NO: 96).

FIG. 15 shows a comparison of the amino acid sequence of Tbp2 from H. influenzae strains Eagan, DL63, PAK 12085, SB12, SB29, SB30 and SB32 (SEQ ID NOS: 8, 6, 12, 109, 110, 112, 114), N. meningitidis strains B16B6 and M982 (SEQ ID NOS: 97 and 98), N. gonorrhoeae strain FA19, and Actinobacillus pleuropneumoniae strains AP205 and AP37 (SEQ ID NOS: 99 and 100).

FIG. 16A shows the predicted secondary structure of H. influenzae Tbp1 protein and FIG. 16B shows the predicted secondary structure of H. influenzae Tbp2 protein.

FIG. 17 shows the construction scheme of plasmid JB-1468-29 which expresses H. influenzae type b Eagan Tbp1 from E. coli.

FIG. 18 shows the construction scheme of plasmid JB-1424-2-8 which expresses H. influenzae type b Eagan Tbp2 from E. coli.

FIG. 19 shows the oligonucleotide pairs (SEQ ID NOS: 130, 131) used to construct plasmid JB-.1424-2-8.

FIG. 20 shows the sequence of oligonucleotide pairs A (SEQ ID NOS: 86, 87), B (SEQ ID NOS: 88, 89), C (SEQ ID NOS: 90, 91) and D (SEQ ID NOS: 92, 93) for constructing Tbp1 and Tbp2 expression plasmids.

FIG. 21 shows the construction scheme of plasmid JB-1600-1 which expresses H. influenzae strain SB12 Tbp2 from E. coli.

FIG. 22 shows SDS-PAGE gels of products from the expression of Haemophilus type b Eagan Tbp1 protein, Eagan Tbp2 protein, and non-typable H. influenzaea SB12 Tbp2 protein from E. coli. Lane 1, JB-1476-2-1 (T7/Eagan Tbp1) at t_(o) ; lane 2, JB-1476-2-1 at t=4h induction; lane 3, molecular weight markers of 200 kDa, 116 kDa, 97.4 kDa, 66 kDa, 45 kDa and 31 kDa; lane 4, JB-1437-4-1 (T7/Eagan Tbp2) at t_(o) ; lane 5, JB-1437-4-1 at t=4h induction; lane 6, JB-1607-1-1 (T7/SB12 Tbp2) at t_(o) ; lane 7, JB-1607-1-1 at t=4h induction.

FIG. 23 shows a purification scheme for recombinant Tbp1 and Tbp2 expressed from E. coli.

FIG. 24, comprising panels A and B, shows an analysis of the purity of recombinant Tbp1 and Tbp2 purified by the scheme of FIG. 23. Lane 1 contains molecular weight size markers (106, 80, 49.5, 32.5, 27.5 and 18.5 kDa), Lane 2 is E. Coli whole cell lysate. Lane 3 is solubilized inclusion bodies. Lane 4 is purified Tbp1 or Tbp2.

FIG. 25, comprising panels A and B, shows the immunogenicity of rTbp1 (upper (A) panel) and rTbp2 (lower (B) panel) in mice.

FIG. 26 shows the reactivity of anti-Eagan rTbp1 antisera with various H. influenzae strains on a Western blot. Lane 1, BL21/DE3; lane 2, SB12-EDDA; lane 3, SB12+ EDDA; lane 4, SB29 -EDDA; lane 5, SB29 +EDDA; lane 6, SB33 -EDDA; lane 7, SB33 +EDDA; lane 8, Eagan -EDDA; lane 9, Eagan +EDDA; lane 10, B. catarrhalis 4223 -EDDA; lane 11, B. catarrhalis 4223 +EDDA; lane 12, N. meningitidis 608 -EDDA; lane 13, N. meningitidis 608 +EDDA; lane 14, induced JB-1476-2-1 expressing recombinant Eagan Tbp1; lane 15, molecular weight markers. Specific˜95 kDa bands reacted with the anti-Tbp1 antisera in lanes 3, 4, 5, 7, 8 and 9, corresponding to H. influenzae strains SB12, SB29, SB33 and Eagan; ˜110 kDa bands in lanes 10 and 11, corresponding to B. catarrhalis strain 4223; and ˜80 kDa bands in lanes 12 and 13, corresponding to N. meningitidis 608.

FIG. 27 shows the reactivity of anti-Eagan rTbp2 antisera with various H. influenzae strains on a Western blots. Lane 1, molecular weight markers; lane 2, induced JB-1437-4-1 expressing recombinant Eagan Tbp2; lane 3, SB12-EDDA; lane 4, SB12 +EDDA; lane 5, SB29 -EDDA; lane 6, SB29 +EDDA; lane 7, SB30 -EDDA; lane 8, SB30 +EDDA; lane 9, SB32 -EDDA; lane 10, SB33-EDDA; lane 11, SB33 +EDDA; lane 12, PAK -EDDA; lane 13, PAK +EDDA; lane 14, Eagan -EDDA; lane 15, Eagan +EDDA. Specific bands of 60-70 kDa were reactive with the anti-Tbp2 antisera in lanes, 3, 6, 7, 8, 13, 14 and 15, i.e. strains SB12, SB29, SB30, PAK and Eagan.

FIG. 28 shows the construction of plasmids pUHIT1KFH and pUHIT1KFP used to generate strains of H. influenzae that do not produce transferrin receptor.

FIG. 29 shows the construction of plasmids encoding chimeric polioviruses expressing an epitope derived from transferrin receptor protein that is conserved among bacteria that produce transferrin receptor protein.

FIG. 30 is a Western blot showing the reactivity of antisera produced by immunization of rabbits with poliovirus chimeras expressing an epitope derived from transferrin receptor protein that is conserved among bacteria that produce transferrin receptor protein. Panel A shows a Coomassie Brilliant Blue-stained gel showing purified recombinant Tbp2 from H. influenzae strain SB12 expressed in E. coli (lane 1), purified Tbp2 from Branhamella catarrhalis strain 4223 (lane 2), a whole cell lysate of iron-limited B. catarrhalis strain 4223 (lane 3), a whole cell lysate of E. coli JM109 grown under non-iron limited conditions (lane 5). Panel B shows results of a Western blot of a replicate gel using a pool of the sera collected on day 27 from rabbits immunised with PV1TBP2A (rabbits 40, 41 and 42). Panel C shows the results for a pool of prebleed sera from the same, which displayed minimal specific reactivity.

In some of the above Figures, the following abbreviations have been used to designate particular site specific restriction endonucleases: R, Eco RI; Ps, Pst I; H, Hind III; Bg, Bgl II; Nde, Nde I; Ear, Ear I; and Sau, Sau3A I.

In FIG. 28, the following abbreviations have been used to designate particular site specific restriction endonucleases: A, Acc I; B Bam HI; E, Eco RI; O, Xho I; H, Hind III; Ps, Pst I; V, Eco RV; X, Xba I, G, Bgl II; S, Sal I; K, Kpn I; and S*, Sac I.

GENERAL DESCRIPTION OF THE INVENTION

Any Haemophilus strain may be conveniently used to provide the purified and isolated nucleic acid which may be in the form of DNA molecules, comprising at least a portion of the nucleic acid coding for a transferrin receptor as typified by embodiments of the present invention. Such strains are generally available from clinical sources and from bacterial culture collections, such as the American Type Culture Collection.

According to an aspect of the invention, the transferrin receptor protein may be isolated from Haemophilus strains by the methods described by Schryvers (1989), Ogunnaviwo and Schryvers (1992) and U.S. Pat. No. 5,141,743, the subject matter of which is hereby incorporated by reference. Although the details of an appropriate process are provided in U.S. Pat. No. 5,141,743, a brief summary of such process is as follows. Isolation of transferrin receptor is achieved by isolating a membrane fraction from a bacterial strain expressing transferrin binding activity and purifying the transferrin receptor by an affinity method involving the sequential steps of prebinding of transferrin to the transferrin receptor in the membrane fraction, solubilising the membrane, immobilising the transferrin and separating the transferrin receptor from the immobilised transferrin. Alternatively, the receptor proteins may be isolated by a modification of the above method in which the prebinding step is avoided and a high concentration of salt is included in the solubilization buffer to allow direct isolation with immobilized transferrin as described in Ogunnariwo and Schryvers (1992).

In this application, the term "transferrin receptor" is used to define a family of Tbp1 and/or Tbp2 proteins which includes those having variations in their amino acid sequences including those naturally occurring in various strains of, for example, Haemophilus. Other bacterial sources of transferrin receptor include, but are not limited to, species of Neisseria, Branhamella, Pasteurella and Actinobacillus. Some, if not all, of these bacteria contain both Tbp1 and Tbp2. The purified and isolated DNA molecules comprising at least a portion coding for transferrin receptor of the present invention also include those encoding functional analogs of transferrin receptor. In this application, a first protein or peptide is a "functional analog" of a second protein if the first protein is immunologically related to and/or has the same function as the second protein or peptide. The functional analog may be, for example, a fragment of the protein or a substitution, addition or deletion mutant thereof.

In one particular embodiment, the transferrin receptor was isolated from H. influenzae type b strain DL63 and purified by affinity chromatography methods, as described by Schryvers (1989), Ogunnariwo and Schryvers (1992) and in U.S. Pat. No. 5,141,743. The isolated and purified transferrin receptor was used to generate anti-TfR antisera in rabbits. Chromosomal DNA from H. influenzae type b strain DL63 was mechanically sheared, EcoRI linkers added, and a λZAP expression library constructed. The library was screened with the anti-TfR rabbit antisera and two positive clones (PBHIT1 and pBHIT2) were obtained which had overlapping restriction maps (FIG. 1A and FIG. 2). The clones were sequenced and two large open reading frames were identified (FIG. 2). The nucleotide sequences of the transferrin receptor genes Tbp1 and Tbp2 (SEQ ID NO: 1) from H. influenzae DL63 and their deduced amino acid sequences (SEQ ID NO: 5 - Tbp1 and SEQ ID NO: 6 - Tbp2) are shown in FIG. 3. The sequence analysis showed the TfR operon to consist of two genes (Tbp1 and Tbp2) arranged in tandem and transcribed from a single promoter (as particularly shown in FIG. 2 and FIG. 3). The Tbp2 protein tends to vary in molecular weight depending on the species whereas the Tbp1 protein tends to have a more consistent molecular weight with some variability across the various bacteria which have TfR genes. The molecular weight of Tbp1 is usually in the range of 94 to 106,000 whereas the molecular weight of Tbp2 varies considerably from 58 to 98 000.

Amino acid sequencing of the N-termini and cyanogen bromide fragments of transferrin receptor from H. influenzae DL63 was performed. The N-terminus of Tbp2 was blocked but amino acid sequences were identified by sequencing of Tbp1 and are indicated by underlining within the protein sequence of FIG. 3. These peptide sequences are Glu Thr Gln Ser lle Lys Asp Thr Lys Glu Ala lle Ser Ser Glu Val Asp Thr (as shown in FIG. 3, SEQ ID NO: 101) and Leu Gln Leu Asn Leu Glu Lys Lys lle Gln Gln Asn Trp Leu Thr His Gln lle Ala Phe (as shown in FIG. 3; SEQ ID NO: 102). The signal sequence of Tbp1 and the putative signal sequence of Tbp2 are indicated by double overligning in FIG. 3. The putative signal sequence for Tbp1 is Met Thr Lys Lys Pro Tyr Phe Arg Leu Ser Ile Ile Ser Cys Leu Leu Ile Ser CYS Tyr Val Lys Ala (SEQ ID NO: 103). The putative signal sequence for Tbp2 is Met Lys Ser Val Pro Leu Ile Ser Gly Gly Leu Ser Phe Leu Leu Ser Ala (SEQ ID NO: 104). The derived amino acid sequence of the N-terminal region of Tbp2 indicates that it is a lipoprotein.

Chromosomal DNA from H. influenzae type b strain Eagan was prepared and libraries were generated. The first library was constructed from DNA partially digested with Sau3A I, size-fractionated for ˜5-10 kb fragments, and cloned into a pUC-based plasmid. The second library was constructed from Eco RI- restricted chromosomal DNA fragments cloned into λZAP. Both libraries were probed with a 5'-fragment of the pBHIT clone as shown in FIG. 2 and partial clones of the TfR genes of H. influenzae Eagan termed S-4368-3-3 and JB-901-5-3 were obtained. Thus, referring to FIGS. 1B and 2, there is illustrated according to further aspects of the present invention, plasmid clones S-4368-3-3 and JB-901-5-3 encoding Tbp1 and Tbp2 from H. influenzae type b strain Eagan. The DNA sequences of the Tbp1 and Tbp2 genes (SEQ ID NO: 2) from H. influenzae type b strain Eagan and their deduced amino acid sequences (SEQ ID NOS: 7 and 8) are shown in FIG. 4 with the Tbp2 sequence being the first gene in the operon. In FIG. 4, putative -35, -10 and ribosomal binding site sequences are overlined.

Chromosomal DNA from H. influenzae type b strain MinnA was prepared and the DNA partially digested with Sau3A I, size-fractionated for 10-20 kb fragments, and cloned into the BamHI site of EMBL3. The library was probed with the 5'-fragment of the pBHIT clone (FIG. 2) and a full-length clone encoding TfR (DS-712-1-3) was obtained. Referring to FIGS. 1C and 2, there is illustrated according to additional aspects of the present invention, plasmid clone DS 712-1-3 encoding Tbp1 and Tbp2 from H. influenzae type b strain MinnA. The DNA sequences of Tbp1 and Tbp2 (SEQ ID NO: 3) and their deduced amino acid sequences (SEQ ID NO: 9 - Tbp1 and SEQ ID NO: 10 - Tbp2) from H. influenzae type b strain MinnA are shown in FIG. 5 where the Tbp2 sequence is first in the operon. In FIG. 5, Putative -35, -10 and ribosomal binding site sequences are overlined.

Chromosomal DNA from the non-typable H. influenzae strain PAK 12085 was prepared. The DNA was partially digested with Sau3A I, size-fractionated for 10-20 kb fragments, and cloned into the BamH I site of EMBL3. The library was probed with the fragments of the PBHIT clone (FIG. 2) and a full-length clone encoding TfR (JB-1042-7-6) was obtained. The restriction map of clone JB-1042-7-6 is shown in FIGS. 1D and 2 and the nucleotide sequences of the Tbp1 and Tbp2 genes (SEQ ID NO: 4) from H. influenzae PAK 12085 and their deduced amino acid sequences are shown in FIG. 6 (SEQ ID NOS: 11, 12), with the Tbp2 sequence first. In FIG. 6, Putative -35, -10 and ribosomal binding site sequences are overlined.

Chromosomal DNA from the otitis-media derived non-typable H. influenzae strain SB33 was prepared. The DNA was partially digested with Sau3A I, size-fractionated for 10-20 kb fragments, and cloned into the BamH I site of EMBL3. The library was probed with the fragments of the PBHIT clone (FIG. 2) and a full-length clone encoding TfR (JB-1031-2-9) was obtained. The restriction map of clone JB-1031-2-9 is shown in FIG. 2 and the nucleotide sequences of the Tbp1 and Tbp2 genes (SEQ ID NO: 105) from H. influenzae SB33 and their deduced amino acid sequences are shown in FIG. 7 (SEQ ID NOS: 106, 107), with the Tbp2 sequence first. The SB33 tbp2 gene was found to have a single base deletion which resulted in a frame-shift at residue 126 and premature truncation of the resulting protein at residue 168.

PCR amplification of the tbp2 genes from otitis media-derived NTHi strains SB12, SB29, SB30 and SB32 was performed and the genes sequenced.

The nucleotide sequence of the tbp2 genes from non-typable H. influenzae strains SE12 (SEQ ID NO: 105), SB29 (SEQ ID NO: 108), SB30 (SEQ ID NO: 110) and SB32 (SEQ ID NO: 112) are shown in FIGS. 8, 9, 10 and 11 respectively.

All of the amplified tbp2 genes were found to encode full-length Tbp2 proteins indicating that the defective tbp2 gene of strain SB33 was atypical.

The three H. influenzae b strains all had identical short intergenic sequences of only 13 bp between tbp2 and tbp1, but the NTHi strains PAK 12085 and SB33 had longer intergenic sequences of 27 bp (FIG. 12).

Strain SB12 had a 13 bp intergenic sequence identical to that found in the H. influenzae b strains while strains SB29, SB30 and SB32 contained longer intergenic sequences (27-30 bp) as found in the other NTHi strains PAK 12085 and SB33 (FIG. 2B). All nine strains have a common core conserved 13 bp sequence between their tbp2 and tbp1 genes.

A pentapeptide sequence near the amino terminus of H. influenzae Tbp1 was identified (FIG. 12) which is similar to the TonB box. The tonB gene of H. influenzae has been recently cloned and sequenced (Jarosik et al., 1994).

The amino acid sequences of Tbp1 from H. influenzae strains Eagan/MinnA, DL63, PAK 12085 and SB33 strains are compared in FIG. 14. The Tbp1 proteins of Eagan and MinnA are identical and 912 amino acids in length, that of DL63 has 914 residues, that of PAK 12085 has 914 residues, and that of SB33 has 911 residues. The H. influenzae Tbp1 proteins are highly conserved with 95-100% sequence identity. The amino acid sequences of Tbp2 from H. influenzae strains Eagan/MinnA, DL63, PAK 12085 SB12, SB29, SB30 and SB32 are compared in FIG. 15. The Tbp2 proteins of Eagan and MinnA are identical and contain 660 amino acids, that of DL63 has 644 residues, and that of PAK 12085 has 654 residues. There is a single base deletion in the SB33 tbp2 gene which results in a frame-shift at residue 126 and premature trunction of the resulting protein at residue 168. The missing base was confirmed by direct sequencing of PCR amplified chromosomal DNA. With the exception of Eagan and MinnA which are identical, the Tbp2 protein sequences are less conserved with only 66-70% identity, but there are several short segments of conserved sequence which can be identified in FIG. 15. The PCR amplified thp2 genes from strains SB12, SB29, SB30 and SB32 were all found to encode full-length Tbp2 proteins. There was sequence and size heterogeneity amongst the deduced Tbp2 proteins wherein SB12 had 648 amino acids, SB29 had 631 residues, SB30 had 630 residues and SB32 had 631 residues.

Putative secondary structures of Eagan Tbp1 and Tbp2 were determined (FIGS. 16A and 16B). Both proteins have several transmembrane domains, with Tbp1 traversing the membrane 20 times and Tbp2 crossing it 12 times. Three exposed conserved epitopes were identified in the Tbp1 amino-terminal region (DNEVTGLGK - SEQ ID NO: 43, EQVLN/DIRDLTRYD - SEQ ID NOS: 139 and 140, and GAINEIEYENVKAVEISK - SEQ ID NO: 141) and one in the C-terminal region (GI/VYNLF/LNYRYVTWE - SEQ ID NOS: 142 and 143). Only three small conserved regions can be identified within the Tbp2 proteins of the human pathogens: CS/LGGG(G)SFD - SEQ ID NOS: 75, 144 and 145 at the N-terminal, LE/SGGFY/FGP - SEQ ID NOS: .74 and 146 located internally, and WFGAR/K - SEQ ID NOS: 83 and 84 at the C-terminus.

The discovery that the Tbp2 amino acid sequence varies between strains of Haemophilus allows for the grouping of Haemophilus into sub-groups defined by the same Tbp2 amino acid sequence. This discovery allows the rational selection of a minimal number of Tbp1 and/or Tbp2 sequences or synthetic peptides representing epitopes shared by such subtypes within strains of Haemophilus to be used in immunogenic compositions for, for example, immunization against the diseases caused by Haemophilus and other bacteria that produce transferrin receptor with sequence similarities to Tbp1 and Tbp2 from Haemophilus species. Thus, a minimal number of transferrin receptor, analogs, fragments, and/or peptides, may be used to immunize against many or all strains of Haemophilus and other bacterial pathogens that produce transferrin receptor.

Furthermore, the amino acid sequences of the transferrin receptor from a range of bacterial pathogens (H. influenzae type b, non-typable H. influenzae, Neisseria meningitidis, Neisseria gonorrhoeae and Actinobacillus (Haemophilus) pleuropneumoniae) were compared as shown in FIGS. 14 and 15. This analysis revealed regions of Tbp1 and Tbp2 which are conserved between all of these bacteria. Some of such conserved sequences are contained in peptides in Tables 2 and 3. In particular the sequences DNEVTGLGK (SEQ ID: 43), EQVLNIRDLTRYDPGI (SEQ ID NO: 44), EQVLNIRDLTRYDPGISVVEQG RGASSGYSIRGMD (SEQ ID NO: 45), GAINEIEYENVKAVEISKG (SEQ ID NO: 46) and GALAGSV (SEQ ID NO: 47) are conserved in Tbp1 (Table 1 and FIG. 14). Particular conserved sequences in Tbp2 include LEGGFYGP (SEQ ID NO: 74), CSGGGSFD (SEQ ID NO: 75), YVYSGL (SEQ ID NO: 76), CCSNLSYVKFG (SEQ ID NO: 77), FLLGHRT (SEQ ID NO: 78), EFNVOF (SEQ ID NO: 79), NAFTGTA (SEQ ID NO: 80), VNGAFYG (SEQ ID NO: 81), ELGGYF (SEQ ID NO: 82), VVFGAR (SEQ ID NO: 83) and VVFGAK (SEQ ID NO: 84) (Table 2 and FIG. 15).

The discovery of conserved sequences within the transferrin receptor of a range of bacterial pathogens allows the selection of a minimal number of antigens having particular amino acid sequences (including in the form of synthetic peptides) to immunize against the disease caused by pathogens that have transferrin receptors. Such bacteria in addition to those recited above include other species of Neisseria, such as Neisseria gonorrhoeae, and Branhamella, including Branhamella catarrhalis. Such conserved amino acid sequences among many bacterial pathogens permits the generation of TfR specific antibodies, including monoclonal antibodies, that recognize most if not all transferrin receptors. Antiserum was raised against peptides corresponding to conserved portions of the transferrin receptor. This antiserum recognized the transferrin receptor in Branhamella catarrhalis. Such antisera are useful for the detection and neutralization of most if not all bacteria that produce TfR protein and are also useful for passive immunization against the diseases caused by such pathogens. Diagnostic assays and kits using such conserved amino acid sequences are useful to detect many if not all bacteria that produce transferrin receptor.

Epitopes containing the afore-mentioned amino acid sequences can be delivered to cells of the immune system by the use of synthetic peptides containing such sequences, or by the use of live vectors expressing such sequences, or by the direct administration of nucleic acid molecules encoding the amino acid sequence.

Some peptides containing conserved amino acid sequences within the Tbp1 proteins of H. influenzae type b strains Eagan, MinnA, DL63 and the nontypable strain PAK 12085 are shown in Table 2. Antibodies to some of these peptides were raised in guinea pigs (Table 4). Peptides containing conserved amino acid sequences within the Tbp2 proteins of H. influenzae type b strains Eagan, Minn A, DL63 and the nontypable strain PAK 12085 are shown in Table 3. Antibodies to some of these peptides were raised in guinea pigs (Table 4).

The coding sequences of the Tbp1 and Tbp2 genes may be cloned into appropriate expression vectors to produce recombinant proteins. Recombinant Tbp1 and Tbp2 were expressed from E. coli using the T7 expression system. The tbpl gene encoding the mature Eagan Tbp1 protein was cloned in-frame behind the T7 promoter generating plasmid JB-1468-29, as shown in FIG. 17. When introduced into BL21/DE3 cells and induced with IPTG or lactose, Eagan Tbp1 protein was expressed as shown in FIG. 22.

The thp2 gene encoding the mature Tbp2 protein was cloned in-frame behind the T7 promotor generating plasmid JB-1424-2-8 as shown in FIG. 18. When introduced into E. coli cells and induced as above, Tbp2 protein was expressed as shown in FIG. 22.

The tbp2 gene from strain NTHi SB12 was amplified by PCR. The resultant amplified DNA contains the authentic H. influenzae Tbp2 signal sequence before the mature protein. The SB12 tbp2 gene encoding the signal sequence and the mature protein was cloned into the pT7-7 expression system as shown in FIG. 21. When the resultant plasmid (JB-1600-1) was introduced into E. coli BL21/DE3 cells and induced, SB12 Tbp2 was expressed, as shown in FIG. 22.

Recombinant proteins Tbp1 and Tbp2 produced in E. coli as inclusion bodies were purified by the scheme shown in FIG. 23. The purified proteins were at least about 70% pure as shown in FIG. 24. Immunogenicity studies were performed in mice with the purified recombinant Tbp1 and Tbp2 proteins. Both proteins elicited a good immune response in mice at 3-10 μg doses (FIG. 25).

Antisera raised to recombinant Tbp1 or Tbp2 derived from one H. influenzae strain are cross-reactive with other strains, making these potentially useful diagnostic reagents (FIGS. 26 and 27).

Plasmids pUHIT1KFH and pUHITKFP shown in FIG. 28, contain a selectable antibiotic resistance marker cloned within the transferrin receptor operon and were constructed to insertionally inactivate the transferrin receptor operon. These plasmids were used to transform Haemophilus to generate strains that do not produce transferrin receptor Tbp1 and/or Tbp2 as described in Example 19. Such strains are useful as negative controls (since they do not produce TfR) in in vitro and in vivo detection and diagnostic embodiments. Such strains are also expected to be attenuated for in vivo growth and are useful as live vaccines to provide protection against diseases caused by Haemophilus.

As discussed above, epitopes of transferrin receptor proteins can be delivered to cells of the immune system by the use of live vectors expressing such amino acid sequences and the live vector may be poliovirus. Referring to FIG. 29 there is illustrated the construction of hybrid polioviruses expressing an epitope of transferrin receptor protein including the conserved epitope from Tbp2 LEGGFYGP (SEQ ID NO: 74). Such viruses were recognized by antibodies raised against a peptide incorporating the amino acid sequence LEGGFYGP (SEQ ID NO: 74) (Table 5) indicating that the viruses expressed this sequence in an antigenically recognisable form. PV1TBP2A and PV1TBP2B were also neutralized by rabbit antisera raised against H. influenzae strain DL63 tbp2, indicating that at least these two viruses expressed the sequence in a form recognisable to antibodies raised against the protein. All viruses were neutralisable by anti-PV1 sera, indicating that the changes in polio neutralization antigenic site I had not significantly affected other antigenic sites on the viruses. Furthermore, rabbit antiserum produced by immunization with poliovirus chimera PV1TBP2A or PV1TBP2B recognized a peptide incorporating the amino acid sequence LEGGFYGP (SEQ ID NO: 74). This indicates that the sequences expressed by PV1TB2A and PV1TBP2B are immunogenic and elicit antibodies capable of recognizing the same sequence in the context of a synthetic peptide.

Referring to FIG. 30, panel A shows an SDS PAGE gel showing purified recombinant thp2 from H. influenzae strain SB12 expressed in E. coli (lane 1), tbp2 from Branhamella catarrhalis strain 4223 (lane 2), a whole cell lysate of iron-limited B. catarrhalis strain 4223 (land 3) , a whole cell lysate of iron-limited E. coli JM109 (lane 4), and a whole cell lysate of E. coli JM109 grown under non-iron limited conditions (lane 5). Panel B shows results of a Western blot of a replicate gel using a pool of sera from rabbits immunized with PV1TBP2A. There was a strong reaction with the purified transferrin-binding proteins in lanes 1 and 2, and with a similar sized band in lane 3. There was no significant reaction with any E. coli proteins (lanes 4 and 5). Panel C shows the results for a pool of prebleed sera from the same rabbits, which displayed minimal specific reactivity. These results show that PV1TBP2A is able to induce antisera specific for transferrin binding proteins from H. influenzae and B. catarrhalis, and that the antisera can distinguish B. catarrhalis from E. coli, which does not express an equivalent protein.

The purified and isolated DNA molecules comprising at least a portion coding for a transferrin receptor of a species of Haemophilus typified by the embodiments described herein are advantageous as:

nucleic acid probes for the specific identification of Haemophilus strains in vitro or in vivo.

the products encoded by the DNA molecules are useful as diagnostic reagents, antigens for the production of Haemophilus-specific antisera, for vaccination against the diseases caused by species of Haemophilus and (for example) detecting infection by Haemophilus.

peptides corresponding to portions of the transferrin receptor as typified by the embodiments described herein are advantageous as diagnostic reagents, antigens for the production of Haemophilus-specific antisera, for vaccination against the diseases caused by species of Haemophilus and (for example) for detecting infection by Haemophilus.

The transferrin receptor encoded by the nucleic acid molecules of the present invention, fragments and analogs thereof, and peptides containing sequences corresponding to portions of the transferrin receptor that are conserved between various isolates of Haemophilus and other bacteria that produce transferrin receptor, are useful in diagnosis of and immunization against diseases caused by any bacterial strain that produces transferrin receptor. In particular, peptides containing the sequences LEGGFYGP (SEQ ID NO: 74) are conserved in the transferrin receptor proteins of many bacterial pathogens that produce transferrin receptor and are appropriate for diagnosis of and immunization against diseases caused by bacteria that produce transferrin receptor. Such bacteria include but are not limited to species of Haemophilus, Neisseria (including N. meningitidis and N. gonorrhoeae) and Branhamella (including B. catarrhalis).

It is clearly apparent to one skilled in the art, that the various embodiments of the present invention have many applications in the fields of vaccination, diagnosis, treatment of, for example, Haemophilus infections, and infections with other bacterial pathogens that produce transferrin receptor and the generation of immunological reagents. A further non-limiting discussion of such uses is further presented below.

1. Vaccine Preparation and Use

Immunogenic compositions, suitable to be used as vaccines, may be prepared from immunogenic transferrin receptor, analogs and fragments thereof and/or peptides as disclosed herein. The vaccine elicits an immune response which produces antibodies, including anti-transferrin receptor antibodies and antibodies that are opsonizing or bactericidal. Should the vaccinated subject be challenged by Haemophilus or other bacteria that produce a transferrin receptor, the antibodies bind to the transferrin receptor and thereby prevent access of the bacteria to an iron source which is required for viability. Furthermore, opsonizing or bactericidal anti-TfR antibodies may also provide protection by alternative mechanisms.

Vaccines containing peptides are generally well known in the art, as exemplified by U.S. Pat. Nos. 4,601,903; 4,599,231; 4,599,230; and 4,596,792; all of which references are incorporated herein by reference. Immunogenic compositions including vaccines may be prepared as injectables, as liquid solutions or emulsions. The transferrin receptor, analogs and fragments thereof and/or peptides may be mixed with pharmaceutically acceptable excipients which are compatible with the transferrin receptor, fragments analogs or peptides. Such excipients may include, water, saline, dextrose, glycerol, ethanol, and combinations thereof. The immunogenic compositions and vaccines may further contain auxiliary substances such as wetting or emulsifying agents, pH buffering agents, or adjuvants to enhance the effectiveness of the vaccines. Immunogenic compositions and vaccines may be administered parenterally, by injection subcutaneously or intramuscularly. Alternatively, the immunogenic compositions formed according to the present invention, may be formulated and delivered in a manner to evoke an immune response at mucosal surfaces. Thus, the immunogenic composition may be administered to mucosal surfaces by, for example, the nasal or oral (intragastric) routes. The immunogenic composition may be provided in combination with a targeting molecule for delivery to specific cells of the immune system or to mucosal surfaces. Some such targeting molecules include strain B12 and fragments of bacterial toxins, as described in WO 92/17167 (Biotech Australia Pty. Ltd.), and monoclonal antibodies, as described in U.S. Pat. No. 5,194,254 (Barber et al). Alternatively, other modes of administration including suppositories and oral formulations may be desirable. For suppositories, binders and carriers may include, for example, polyalkalene glycols or triglycerides. Oral formulations may include normally employed incipients such as, for example, pharmaceutical grades of saccharine, cellulose and magnesium carbonate. These compositions take the form of solutions, suspensions, tablets, pills, capsules, sustained release formulations or powders and contain 10-95% of the transferrin receptor, fragment analogs and/or peptides.

The vaccines are administered in a manner compatible with the dosage formulation, and in such amount as will be therapeutically effective, protective and immunogenic. The quantity to be administered depends on the subject to be treated, including, for example, the capacity of the individual's immune system to synthesize antibodies, and if needed, to produce a cell-mediated immune response. Precise amounts of active ingredient required to be administered depend on the judgment of the practitioner. However, suitable dosage ranges are readily determinable by one skilled in the art and may be of the order of micrograms of the transferrin receptor, analogs and fragments thereof and/or peptides. Suitable regimes for initial administration and booster doses are also variable, but may include an initial administration followed by subsequent administrations. The dosage of the vaccine may also depend on the route of administration and will vary according to the size of the host.

The nucleic acid molecules encoding the transferrin receptor of the present invention may also be used directly for immunization by administration of the DNA directly, for example by injection for genetic immunization or by constructing a live vector such as Salmonella, BCG, adenovirus, poxvirus, vaccinia or poliovirus. A discussion of some live vectors that have been used to carry heterologous antigens to the immune system are discussed in for example O'Hagan (1992). Processes for the direct injection of DNA into test subjects for genetic immunization are described in, for example, Ulmer et al., 1993.

The use of peptides in vivo may first require their chemical modification since the peptides themselves may not have a sufficiently long serum and/or tissue half-life and/or sufficient immunogenicity. Such chemically modified peptides are referred to herein as "peptide analogs". The term "peptide analog" extends to any functional chemical equivalent of a peptide characterized by its increased stability and/or efficacy and immunogenicity in vivo or in vitro in respect of the practice of the invention. The term "peptide analog" is also used herein to extend to any amino acid derivative of the peptides as described herein. Peptide analogs contemplated herein are produced by procedures that include, but are not limited to, modifications to side chains, incorporation of unnatural amino acids and/or their derivatives during peptide synthesis and the use of cross-linkers and other methods which impose conformational constraint on the peptides or their analogs.

Examples of side chain modifications contemplated by the present invention include modification of amino groups such as by reductive alkylation by reaction with an aldehyde followed by reduction with NaBH₄ ; amidation with methylacetimidate; acetylation with acetic anhydride; carbamylation of amino groups with cyanate; trinitrobenzylation of amino groups with 2, 4, 6, trinitrobenzene sulfonic acid (TNBS); alkylation of amino groups with succinic anhydride and tetrahydrophthalic anhydride; and pyridoxylation of lysine with pyridoxal-5'-phosphate followed by reduction with NaBH₄.

The guanidino group of arginine residues may be modified by the formation of heterocyclic condensation products with reagents such as 2, 3-butanedione, phenylglyoxal and glyoxal.

The carboxyl group may be modified by carbodiimide activation via o-acylisourea formation followed by subsequent derivatisation, for example, to a corresponding amide.

Sulfhydryl groups may be modified by methods such as carboxymethylation with iodoacetic acid or iodoacetamide; performic acid oxidation to cysteic acid; formation of mixed disulphides with other thiol compounds; reaction with maleimide; maleic anhydride or other substituted maleimide; formation of mercurial derivatives using 4-chloromercuribenzoate, 4-chloromercuriphenylsulfonic acid, phenylmercury chloride, 2-chloromercuric-4-nitrophenol and other mercurials; carbamylation with cyanate at alkaline pH.

Tryptophan residues may be modified by, for example, oxidation with N-bromosuccinimide or alkylation of the indole ring with 2-hydroxy-5-nitrobenzyl bromide or sulphonyl halides. Tryosine residues may be altered by nitration with tetranitromethane to form a 3-nitrotyrosine derivative.

Modification of the imidazole ring of a histidine residue may be accomplished by alkylation with iodoacetic acid derivatives or N-carbethoxylation with diethylpyrocarbonate.

Examples of incorporating unnatural amino acids and derivatives during peptide synthesis include, but are not limited to, use of norleucine, 4-amino butyric acid, 4-amino-3-hydroxy-5-phenylpentanoic acid, 6-aminohexanoic acid-, t-butylglycine, norvaline, phenylglycine, ornithine, sarcosine, 4-amino-3-hydroxy-6-methylheptanoic acid, 2-thienyl alanine and/or D-isomers of amino acids.

Immunogenicity can be significantly improved if the antigens are co-administered with adjuvants, commonly used as an 0.05 to 1.0 percent solution in phosphate - buffered saline. Adjuvants enhance the immunogenicity of an antigen but are not necessarily immunogenic themselves. Adjuvants may act by retaining the antigen locally near the site of administration to produce a depot effect facilitating a slow, sustained release of antigen to cells of the immune system. Adjuvants can also attract cells of the immune system to an antigen depot and stimulate such cells to elicit immune responses.

Immunostimulatory agents or adjuvants have been used for many years to improve the host immune responses to, for example, vaccines. Intrinsic adjuvants, such as lipopolysaccharides, normally are the components of the killed or attenuated bacteria used as vaccines. Extrinsic adjuvants are immunomodulators which are typically non-covalently linked to antigens and are formulated to enhance the host immune responses. Thus, adjuvants have been identified that enhance the immune response to antigens delivered parenterally. Some of these adjuvants are toxic, however, and can cause undesirable side-effects, making them unsuitable for use in humans and many animals. Indeed, only aluminum hydroxide and aluminim phosphate (collectively commonly referred to as alum) are routinely used as adjuvants in human and veterinary vaccines. The efficacy of alum in increasing antibody responses to diptheria and tetanus toxoids is will established and, more recently, a HBsAg vaccine has been adjuvanted with alum. While the usefulness of alum is well established for some applications, it has limitations. For example, alum is ineffective for influenza vaccination and inconsistently elicits a cell mediated immune response. The antibodies elicited by alum-adjuvanted antigens are mainly of the IgGl isotype in the mouse, which may not be optimal for protection by some vaccinal agents.

A wide range of extrinsic adjuvants can provoke potent immune responses to antigens. These include saponins complexed to membrane protein antigens (immune stimulating complexes), pluronic polymers with mineral oil, killed mycobacteria and mineral oil, Freund's complete adjuvant, bacterial products, such as muramyl dipeptide (MDP) and lipopolysaccharide (LPS), as well as lipid A, and liposomes.

To efficiently induce humoral immune responses (HIR) and cell-mediated immunity (CMI), immunogens are emulsified in adjuvants. Many adjuvants are toxic, inducing granulomas, acute and chronic inflammations (Freund's complete adjuvant, FCA), cytolysis (saponins and pluronic polymers) and pyrogenicity, arthritis and anterior uveitis (LPS and MDP). Although FCA is an excellent adjuvant and widely used in research, it is not licensed for use in human or veterinary vaccines because of its toxicity.

Desirable characteristics of ideal adjuvants include:

(1) lack of toxicity;

(2) ability to stimulate a long-lasting immune response;

(3) simplicity of manufacture and stability in long-term storage;

(4) ability to elicit both CMI and HIR to antigens administered by various routes, if required;

(5) synergy with other adjuvants;

(6) capability of selectively interacting with populations of antigen presenting cells (APC);

(7) ability to specifically elicit appropriate T_(H) 1 or T_(H) 2 cell-specific immune responses; and

(8) ability to selectively increase appropriate antibody isotype levels (for example, IgA) against antigens.

U.S. Pat. No. 4,855,283 granted to Lockhoff et al on Aug. 8, 1989 which is incorporated herein by reference thereto teaches glycolipid analogues including N-glycosylamides, N-glycosylureas and N-glycosylcarbamates, each of which is substituted in the sugar residue by an amino acid, as immuno-modulators or adjuvants. Thus, Lockhoff et al. 1991 reported that N-glycolipid analogs displaying structural similarities to the naturally-occurring glycolipids, such as glycosphingolipids and glycoglycerolipids, are capable of eliciting strong immune responses in both herpes simplex virus vaccine and pseudorabies virus vaccine. Some glycolipids have been synthesized from long chain-alkylamines and fatty acids that are linked directly with the sugars through the anomeric carbon atom, to mimic the functions of the naturally occurring lipid residues.

U.S. Pat. No. 4,258,029 granted to Moloney, assigned to the assignee hereof and incorporated herein by reference thereto, teaches that octadecyl tyrosine hydrochloride (OTH) functions as an adjuvant when complexed with tetanus toxoid and formalin inactivated type I, II and III poliomyelitis virus vaccine. Also, Nixon-George et al. 1990, reported that octadecyl esters of aromatic amino acids complexed with a recombinant hepatitis B surface antigen, enhanced the host immune responses against hepatitis B virus.

Lipidation of synthetic peptides has also been used to increase their immunogenicity. Thus, Wiesmuller 1989, describes a peptide with a sequence homologous to a foot-and-mouth disease viral protein coupled to an adjuvant tripalmityl-s-glyceryl-cysteinylserylserine, being a synthetic analogue of the N-terminal part of the lipoprotein from Gram negative bacteria. Furthermore, Deres et al. 1989, reported in vivo priming of virus-lpecific cytotoxic T lymphocytes with synthetic lipopeptide vaccine which comprised of modified synthetic peptides derived from influenza virus nucleoprotein by linkage to a lipopeptide, N-palmityl-s-[2,3-bis(palmitylxy)-(2RS)-propyl-[R]-cysteine (TPC).

2. Immunoassays

The transferrin receptor, analogs and fragments thereof and/or peptides of the present invention are useful as immunogens, as antigens in immunoassays including enzyme-linked immunosorbent assays (ELISA), RIAs and other non-enzyme linked antibody binding assays or procedures known in the art for the detection of anti-bacterial, Haemophilus, TfR and/or peptide antibodies. In ELISA assays, the transferrin receptor, analogs, fragments and/or peptides corresponding to portions of TfR protein are immobilized onto a selected surface, for example a surface capable of binding proteins or peptides such as the wells of a polystyrene microtiter plate. After washing to remove incompletely adsorbed transferrin receptor, analogs, fragments and/or peptides, a nonspecific protein such as a solution of bovine serum albumin (BSA) or casein that is known to be antigenically neutral with regard to the test sample may be bound to the selected surface. This allows for blocking of nonspecific adsorption sites on the immobilizing surface and thus reduces the background caused by nonspecific bindings of antisera onto the surface. Preferably, the selected peptides are from the conserved regions of Table 2 or Table 3 to enhance the cross-species detection unless one particular bacterial species is to be detected. In that event, a polypeptide is selected which is unique to the TfR of that particular species. Normally, the peptides are in the range of 12 residues and up and preferably 14 to 30 residues. It is understood however, that a mixture of peptides may be used either as an immunogen in a vaccine or as a diagnostic agent. There may be circumstances where a mixture of peptides from the conserved regions and/or from the non-conserved regions are used to provide cross-species protection and/or diagnosis. In this instance, the mixture of peptide immunogens is commonly referred to as a "cocktail" preparation for use as a vaccine or diagnostic agent.

The immobilizing surface is then contacted with a sample such as clinical or biological materials to be tested in a manner conducive to immune complex (antigen/antibody) formation. This may include diluting the sample with diluents such as BSA, bovine gamma globulin (BGG) and/or phosphate buffered saline (PBS)/Tween. The sample is then allowed to incubate for from 2 to 4 hours, at temperatures such as of the order of 25° to 37° C. Following incubation, the sample-contacted surface is washed to remove non-immunocomplexed material. The washing procedure may include washing with a solution such as PBS/Tween, or a borate buffer.

Following formation of specific immunocomplexes between the test sample and the bound transferrin receptor, analogs, fragments and/or peptides, and subsequent washing, the occurrence, and even amount, of immunocomplex formation may be determined by subjecting the immunocomplex to a second antibody having specificity for the first antibody. If the test sample is of human origin, the second antibody is an antibody having specificity for human immunoglobulins and in general IgG. To provide detecting means, the second antibody may have an associated activity such as an enzymatic activity that will generate, for example, a color development upon incubating with an appropriate chromogenic substrate. Quantification may then achieved by measuring the degree of color generation using, for example, a visible spectra spectrophotometer.

3. Use of Sequences as Hybridization Probes

The nucleotide sequences of the present invention, comprising the sequence of the transferrin receptor gene, now allow for the identification and cloning of the transferrin receptor genes from any species of Haemophilus and other bacteria that have transferrin receptor genes.

The nucleotide sequences comprising the sequence of the transferrin receptor genes of the present invention are useful for their ability to selectively form duplex molecules with complementary stretches of other TfR genes. Depending on the application, a variety of hybridization conditions may be employed to achieve varying degrees of selectivity of the probe toward the other TfR genes. For a high degree of selectivity, relatively stringent conditions are used to form the duplexes, such as low salt and/or high temperature conditions, such as provided by 0.02 M to 0.15 M NaCl at temperatures of between about 50° C. to 70° C. For some applications, less stringent hybridization conditions are required such as 0.15 M to 0.9 M salt, at temperatures ranging from between about 20° C. to 55° C. Hybridization conditions can also be rendered more stringent by the addition of increasing amounts of formamide, to destabilize the hybrid duplex. Thus, particular hybridization conditions can be readily manipulated, and will generally be a method of choice depending on the desired results. In general, convenient hybridization temperatures in the presence of 50% formamide are: 42° C. for a probe which is 95 to 100% homologous to the target fragment, 37° C. for 90 to 95% homology and 32° C. for 85 to 90% homology.

In a clinical diagnostic embodiment, the nucleic acid sequences of the TfR genes of the present invention may be used in combination with an appropriate means, such as a label, for determining hybridization. A wide variety of appropriate indicator means are known in the art, including radioactive, enzymatic or other ligands, such as avidin/biotin, which are capable of providing a detectable signal. In some diagnostic embodiments, an enzyme tag such as urease, alkaline phosphatase or peroxidase, instead of a radioactive tag may be used. In the case of enzyme tags, calorimetric indicator substrates are known which can be employed to provide a means visible to the human eye or spectrophotometrically, to identify specific hybridization with samples containing TfR gene sequences.

The nucleic acid sequences of TfR genes of the present invention are useful as hybridization probes in solution hybridizations and in embodiments employing solid-phase procedures. In embodiments involving solid-phase procedures, the test DNA (or RNA) from samples, such as clinical samples, including exudates, body fluids (e.g., serum, amniotic fluid, middle ear effusion, sputum, bronchoalveolar lavage fluid) or even tissues, is adsorbed or otherwise affixed to a selected matrix or surface. The fixed, single-stranded nucleic acid is then subjected to specific hybridization with selected probes comprising the nucleic acid sequences of the TfR genes or fragments thereof of the present invention under desired conditions. The selected conditions will depend on the particular circumstances based on the particular criteria required depending on, for example, the G+C contents, type of target nucleic acid, source of nucleic acid, size of hybridization probe etc. Following washing of the hybridization surface so as to remove non-specifically bound probe molecules, specific hybridization is detected, or even quantified, by means of the label. As with the selection of peptides, it is preferred to select nucleic acid sequence portions which are conserved among species of Haemophilus, such as nucleic acid sequences encoding the conserved peptide sequence of FIGS. 8, 9, 13 and 14 and particularly listed in Tables 2 and 3. The selected probe may be at least 18 bp and may be in the range of 30 bp to 90 bp long.

4. Expression of the Transferrin Receptor Genes

Plasmid vectors containing replicon and control sequences which are derived from species compatible with the host cell may be used for the expression of the transferrin receptor genes in expression systems. The vector ordinarily carries a replication site, as well as marking sequences which are capable of providing phenotypic selection in transformed cells. For example, E. coli may be transformed using pBR322 which contains genes for ampicillin and tetracycline resistance and thus provides easy means for identifying transformed cells. The pBR322 plasmid, or other microbial plasmid or phage must also contain, or be modified to contain, promoters which can be used by the host cell for expression of its own proteins.

In addition, phage vectors containing replicon and control sequences that are compatible with the host can be used as a transforming vector in connection with these hosts. For example, the phage in lambda GEM™-11 may be utilized in making recombinant phage vectors which can be used to transform host cells, such as E. coli LE392.

Promoters commonly used in recombinant DNA construction include the β-lactamase (penicillinase) and lactose promoter systems (Chang et al., 1978: Itakura et al., 1977 Goeddel et al., 1979; Goeddel et al., 1980) and other microbial promoters such as the T7 promoter system (U.S. Pat. No. 4,952,496). Details concerning the nucleotide sequences of promoters are known, enabling a skilled worker to ligate them functionally with genes. The particular promoter used will generally be a matter of choice depending upon the desired results. Hosts that are appropriate for expression of the transferrin receptor genes, fragment analogs or variants thereof include E. coli, Bacillus species, Haemophilus, fungi, yeast or the baculovirus expression system may be used.

In accordance with this invention, it is preferred to make the protein by recombinant methods, particularly when the naturally occurring TfR protein as purified from a culture of a species of Haemophilus may include trace amounts of toxic materials or other contaminants . This problem can be avoided by using recombinantly produced TfR protein in heterologous systems which can be isolated from the host in a manner to minimize comtaminants in the purified material. Particularly desirable hosts for expression in this regard include Gram positive bacteria which do not have LPS and are therefore endotoxin free. Such hosts include species of Bacillus and may be particularly useful for the production of non-pyrogenic transferrin receptor, fragments or analogs thereof. Furthermore, recombinant methods of production permit the manufacture of Tbp1 or Tbp2 or fragments thereof separate from one another which is distinct from the normal combined proteins present in Haemophilus.

Biological Deposits

Certain plasmids that contain at least a portion coding for a transferrin receptor from strains of Haemophilus influenzae that are described and referred to herein have been deposited with the American Type Culture Collection (ATCC) located at Rockville, Md. USA pursuant to the Budapest Treaty and prior to the filing of this application. Samples of the deposited plasmids will become available to the public upon grant of a patent based upon this United States patent application. The invention described and claimed herein is not to be limited in scope by plasmids deposited, since the deposited embodiment is intended only as an illustration of the invention. Any equivalent or similar plasmids that encode similar or equivalent antigens as described in this application are within the scope of the invention.

Deposit Summary

    ______________________________________                                                      ATCC      Date Deposited                                                                  Clone                Designation    Date Deposited     ______________________________________                                         DS-712-1-3   75603     November 4, 1993                                          JB-1042-7-6           75607         November 4, 1993                           JB-1424-2-8           75937         October 27, 1994                           JB-1600-1             75935         October 27, 1994                           JB-1468-29            75936         October 27, 1994                           pT7TBP2A              75931         October 27, 1994                           pT7TBP2B              75932         October 27, 1994                           pT7TBP2C              75933         October 27, 1994                           pT7TBP2D              75934         October 27, 1994                         ______________________________________                                    

Strains of Haemophilus

Hib strain Eagan is available from Connaught Laboratories Limited, 1755 Steeles Ave. W., Willowdale, Ontario, Canada M2R 3T4.

Hib strain MinnA was obtained from the collection of Dr. Robert Munson, Department of Microbiology and Immunology, Washington University School of Medicine, Children's Hospital, St. Louis, Mo. 63110.

Hib strain DL63 was obtained from the collection of Dr. Eric Hansen, Department of Microbiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Tex. 75235-9048.

PAK 12085 was obtained from the collection of Dr. Robert Munson (supra).

SB12, 29, 30, 32 and 33 were obtained from the collection of Dr. Stephen Barenkamp, Department of Pediatrics, School of Medicine, Saint Louis University Medical Centre, St. Louis, Mo. 63104.

EXAMPLES

The above disclosure generally describes the present invention. A more complete understanding can be obtained by reference to the following specific Examples. These Examples are described solely for purposes of illustration and are not intended to limit the scope of the invention. Changes in form and substitution of equivalents are contemplated as circumstances may suggest or render expedient. Although specific terms have been employed herein, such terms are intended in a descriptive sense and not for purposes of limitations.

Methods of molecular genetics, protein biochemistry, immunology and fermentation technology used but not explicitly described in this disclosure and these Examples are amply reported in the scientific literature and are well within the ability of those skilled in the art.

Example 1

This Example illustrates the preparation of chromosomal DNA from H. influenzae strains DL63, Eagan, MinnA, and PAK 12085, and SB33.

H. influenzae strains were grown on Mueller-Hinton agar or in brain heart infusion broth as described by Harkness et al 1992.

A. Chromosomal DNA extraction from Haemophilus influenzae type b DL63

Chromosomal DNA was prepared as follows. Two hundred and fifty ml of culture were pelleted by centrifugation at 8,000 rpm in a Beckman J14 rotor for 15 minutes. The pellet was washed with 200 ml of SOMM Tris-HCl, pH 8.0, centrifuged as before, resuspended in 12.5 ml of 50 mM Tris-HCl, 50 mM EDTA, pH 8.0, and frozen at -20° C. Then 1.25 ml of a 10 mg/ml lysozyme solution in 0.25M Tris-HCl, pH 8.0, was added to the frozen cell pellet. The pellet was thawed and incubated on ice for 45 minutes. Next, 2.5 ml of a solution of 1 mg/ml proteinase K in 0.5% SDS, 0.4M EDTA, 50 mM Tris-HCl, pH 7.5 was added and the mixture incubated at 50° C. for 1 hour with occasional mixing. The lysate was extracted once with 15 ml of Tris-buffered phenol, then 1.5 ml of 3M sodium acetate and 30 ml of ethanol were added to precipitate the DNA. The DNA was spooled on a glass rod, then dissolved in 12.5 ml of 50 mM Tris-HCl, 1 mM EDTA, pH 7.5 containing 0.2 mg/ml RNAse A by rocking overnight. The sample was extracted once with an equal volume of chloroform, precipitated, and spooled as above. The DNA was dissolved in 2 ml of 50 mM Tris-HCl, 1 mM EDTA, pH 7.5 and stored at 4° C.

B. Chromosomal DNA extraction from Haemophilus influenzae type b Eagan

Fifty ml of culture were pelleted by centrifugation, the pellet resuspended in 25 ml of TE (10 mM Tris, 1 mM EDTA, pH 7.5), and 2×5 ml aliquots used for chromosomal DNA preparation. To each aliquot was added 0.6 ml of 10% sarkosyl and 0.15 ml of 20 mg/ml proteinase K and the samples incubated at 37° C. for 1 hour. The lysate was extracted once with Tris-saturated phenol and three times with chloroform:isoamyl alcohol (24:1). The aqueous phases were pooled for a final volume of 7 ml. Then 0.7 ml of 3M sodium acetate (pH 5.2) and 4.3 ml of isopropanol were added to precipitate the DNA which was spooled, rinsed with 70% ethanol, dried, and resuspended in 1 ml of water.

C. Chromosomal DNA extraction from Haemophilus influenzae Eagan, MinnA, PAX 12085 and SB33

Cells were pelleted from 50 ml of culture by centrifugation at 5000 rpm for 15-20 minutes, at 4° C. The cell pellet was resuspended in 10 ml of TE (10 mM Tris-HCl, 1 mM EDTA, pH 7.5), pronase and SDS were added to final concentrations of 500 μg/ml and 1%, respectively. The sample was incubated at 37° C. for 4 hours until a clear lysate was obtained. The lysate was extracted once with Tris-saturated phenol, once with Tris-saturated phenol/chloroform (1:1), and once with chloroform. The final aqueous phase was dialysed for 24 hours against 2×500 ml of 1M NaCl at 4° C., changing the buffer once, and for 24 hours against 2×500 ml of TE at 4° C., changing the buffer once. The final dialysate was aliquotted for use.

Example 2

This Example illustrates the preparation of chromosomal libraries.

A. H. influenzae DL63-λZAP library

100 μg of H. influenzae DL63 chromosomal DNA in TE was mechanically sheared in a 1 ml syringe with a 25 gauge needle. The sheared DNA was made blunt-ended by adding water to a final volume of 405 μl, 45 μl of 10x S1 nuclease buffer (2M NaCl, 50 mM NaOAc, pH 4.5, 10 mM ZnSO₄, 5% glycerol), and 1.7 μl of S1 nuclease at 100 U/μl and incubating at 37° C. for 15 min. The sample was extracted once with phenol/chloroform and once with chloroform and 1 ml of ethanol was added to precipitate the DNA. The sample was incubated on ice for 10 min or at -20° C. overnight and the DNA was harvested by centrifugation in a microfuge for 30 minutes. The DNA was washed with 70% ethanol and dried. The Eco RI sites in the DNA sequence were methylated using standard procedures. To this methylated DNA was added 5 μl of 100 mM MgCl₂, 8 μl of dNTP mix (2.5 mM each of DATP, dCTP, dGTP, and dTTP), and 4 μl of 5 U/μl Klenow. The mixture was incubated at 12° C. for 30 minutes. 450 μl of STE (0.1M NaCl, 10 mM Tris-HCl, 1 mM EDTA, pH 8.0) were added, and the mixture extracted once with phenol/chloroform, and once with chloroform, before adding 1 ml of ethanol to precipitate the DNA. The sample was incubated on ice for 10 min or at -20° C. overnight. The DNA was harvested by centrifugation in a microfuge for 30 minutes, washed with 70t ethanol and dried.

The DNA was resuspended in 7 μl of TE and to the solution was added 14 μl of phosphorylated Eco RI linkers (200 ng/μl), 3 μl of 10x ligation buffer, 3 μl of 10 mM ATP, and 3 μl of T4 DNA ligase (4 U/μl). The sample was incubated at 4° C. overnight, then incubated at 68° C. for 10 minutes to inactivate the ligase. To the mixture was added 218 μl of H₂ O, 45 μl of 10x Universal buffer, and 7 μl of Eco RI at 30 U/μl. After incubation at 37° C. for 1.5 hours, 1.5 μl of 0.5M EDTA was added, and the mixture placed on ice.

The DNA was size fractionated on a sucrose gradient, pooling fractions containing DNA of 6-10 kb. The pooled DNA was ethanol precipitated and resuspended in 5 μl of TE buffer. 20 ng of insert DNA was ligated for 2-3 days at 4° C. with 1 μg of ZAP II vector in a final volume of 5 μl. The ligation mixture was packaged using GIGAPACK II GOLD (Trademark of Stratagene) and plated on E. coli "SURE (Trademark)" cells on NZY plates. The library was titrated, amplified, and stored at 4° C. under 0.3% chloroform.

B. H. influenzae Eagan-pUC library

Chromosomal DNA prepared from H. influenzae Eagan by the method in Example 1C. was digested with Sau3A I for 2, 5, and 10 minutes and samples electrophoresed on a preparative agarose gel. Gel slices which included DNA fragments between 3-10 kb in length were excised and the DNA extracted by the standard freeze-thaw procedure. Plasmid DNA from pUC 8:2 (pUC 8 with additional Bgl II and Xba I restriction enzyme sites in the multiple cloning site) was digested with BamH I and Bgl II, and dephosphorylated with calf alkaline phosphatase (CAP). The fragments of H. influenzae Eagan DNA were ligated into pUC and the mixture used to transform E. coli JM109 cells.

C. H. influenzae Eagan-λZAP library

Chromosomal DNA from H. influenzae Eagan prepared as in Example 1B was digested with Eco RI and size fractionated on a preparative agarose gel. Gel slices corresponding to DNA fragments of 7-23 kb were excised and DNA was electroeluted overnight in dialysis tubing containing 3 ml of TAE (40 mM Tris-acetate, 1 mM EDTA) at 14V. The DNA was precipitated twice and resuspended in water before being ligated overnight with Eco RI digested λZAP II DNA. The ligation mixture was packaged using the Gigapack II packaging kit (Stratagene) and plated on E. coli XL1-Blue cells. The library was titrated, amplified, and stored at 4° C. under 0.3% chloroform.

D. EMBL3 libraries

H. influenzae MinnA chromosomal DNA (10 μg) was prepared as in Example 1C. and digested with Sau3A I (40 units) for 2, 4, and 6 minutes then size-fractionated on a 10-30% sucrose gradient in TNE buffer (20 mM Tris-HCl, 5 mM NaCl, 1 mM EDTA, pH 8). Fractions containing DNA fragments greater than 5 kb were pooled and precipitated. In a second experiment, chromosomal DNA (2.6 μg) was digested with Sau3A I (4 units) for 1, 2, and 3 minutes and size-fractionated by preparative agarose gel electrophoresis. Gel slices containing DNA fragments of 10-20 kb were excised and DNA extracted by a standard freeze/thaw technique. The size- fractionated DNA from the two experiments was pooled for ligation with BamH I arms of EMBL3 (Promega). The ligation mixture was packaged using the Gigapack II packaging kit and plated on E. coli LE392 cells. The library was titrated, then amplified and stored at 4° C. under 0.3% chloroform.

Chromosomal DNA from H. influenzae PAK 12085 or SB33 prepared as in Example 1C. was digested with Sau3A I (0.5 units/10 μg DNA) at 37° C. for 15 minutes and size-fractionated by agarose gel electrophoresis. Gel slices corresponding to DNA fragments of 15-23 kb were excised and DNA was electroeluted overnight in dialysis tubing containing 3 ml of TAE at 14V. The DNA was precipitated twice and resuspended in water before overnight ligation with EMBL3 BamH I arms (Promega). The ligation mixture was packaged using the Lambda in vitro packaging kit (Amersham) according to the manufacturer's instructions and plated onto E. coli NM539 cells. The library was titrated, then amplified, and stored at 4° C. in the presence of 0.3% chloroform.

Example 3

This Example illustrates screening of the libraries

A. H. influenzae DL63-λZAP expression library

Tbp1 and Tbp2 proteins were affinity purified on solid phase human transferrin (hTf). Briefly, a 20 ml hTf-Sepharose column was prepared according to the manufacturer's protocol for coupling protein ligands to CNBr-activated Sepharose (Sigma). The resulting matrix was washed with 3 column volumes of 50 mM Tris-HCl, 1M NaCl, 6M guanidine-HCl, pH 8.0 to remove non-covalently bound hTf. The column was then equilibrated with 50 mM Tris-HCl, pH 8.0 and bound hTf was iron loaded using 1 ml of 10 mg/ml FeCl₃ in buffer containing 100 mM each of sodium citrate and sodium bicarbonate, pH 8.6, followed by 2 column volumes of 50 mM Tris-HCl, 1 M NaCl, pH 8.0. Total bacterial membranes (300 mg total protein) were prepared from H. influenzae strain DL63 grown on iron deficient media as described previously (Schryvers et al., 1989). Membranes were diluted to 2 mg/ml in 50 mM Tris-HCl, 1M NaCl, pH 8.0 and solubilized by the addition of EDTA to 15 mM and Sarkosyl NL97 to 1.5%. After centrifugation at 40,000×g for 1 hour, the supernatant was applied to the hTf column and the column washed with 10 column volumes of 50 mM Tris-HCl, 1M NaCl, 10 mM EDTA, 0.5% Sarkosyl, pH 8.0. The receptor proteins were eluted using 2M GnHCl in the same buffer and the eluted fractions were dialysed extensively against 25 mM ammonium bicarbonate buffer (5 buffer changes), lyophilized, and stored at -20° C. Isolated proteins were used to generate transferrin receptor-specific antisera in New Zealand White rabbits using standard techniques. Briefly, rabbits were immunized 3 times subcutaneously, at intervals of two weeks, using complete Freund's adjuvant for the first injection and incomplete Freund's adjuvant for subsequent injections.

The DL63 λZAP library was plated on E. coli SURE cells and plaques were transferred onto nitrocellulose membranes which had been pre-soaked in 10 mM IPTG to induce expression from the pBluescript lacZ promoter. Filters were blocked using 0.5% skim milk in 50 mM Tris-HCl, 150 mM NaCl, pH 7.5, prior to being probed with the polyclonal anti-TfR antisera and horse radish peroxidase-conjugated goat anti-rabbit IgG. Plaques were purified by 3 rounds of screening and recombinant pBluescript plasmids (pBHIT1 and pBHIT2; FIGS. 1A and 2) were recovered by the in vivo excision procedure (Short et al., 1988).

B. Eagan, MinnA, and PAK 12085 non-expression libraries

(i) Screening of H. influenzae Eagan-pUC library

Colony lifts onto nitrocellulose were performed using standard techniques and the filters were probed with the 5'pBHIT2 probe of the transferrin receptor gene illustrated in FIG. 2. The probe was labelled with digoxigenin (dig, Boehringer Mannheim) following the manufacturer's specifications. Several putative clones were dot blotted onto nitrocellulose and submitted to second round screening using the same 5'pBHIT2 probe. Second round putatives were analysed by restriction enzyme mapping and clone S-4368-3-3 (FIG. 1B, FIG. 2) was selected for sequence analysis.

(ii) Screening H. influenzae Eagan-λZAP library

The phage library was plated using standard techniques on XLI Blue cells (Stratagene) using LB plates and a 0.7% agarose overlay layer. Plaques were lifted onto nitrocellulose using standard protocols and the filters were baked at 80° C., for 2 hours, under vacuum, to fix the DNA. The 5'pBHIT2 probe of the transferrin receptor gene (FIG. 2) was labelled with digoxigenin and the filters were pre-hybridized for 4 hours at 42° C., then hybridized with the labelled probe at 42° C., overnight. The filters were washed at 68° C. and after autoradiography, several plaques were selected for second round screening. In vivo excision of phagemid DNA from second round putatives was performed according to protocols provided with the λZAP system (Promega). Four clones with identical ˜2.5 kb Eco RI inserts were obtained of which JB-901-5-3 in Figure B, FIG. 2 is an example. Putative plaques were also amplified and phage DNA was purified from 500 ml of culture. Insert DNA was excised by digestion with Xba I and was cloned into puc 8:2 (pUC 8 containing additional Bgl II and Xba I sites in its multiple cloning site) which had been digested with Xba I and dephosphorylated. Clone JB-911-3-2 (FIG. 17) contains the 3'-half of the H. influenzae Eagan TfR operon.

(iii) Screening EMBL 3 libraries

The H. influenzae MinnA library was plated onto LE392 cells on NZCYM plates using 0.7% top agarose in NZCYM as overlay. Plaque lifts onto nitrocellulose filters were performed following standard procedures, and filters were processed and probed with the 5'pBHIT2 probe (FIG. 2) labelled with digoxigenin. Putative plaques were plated and submitted to second and third rounds of screening using the same procedures. Phage DNA was prepared from 500 ml of culture using standard techniques, the insert DNA excised by Sal I digestion, and cloned into pUC to generate clone DS-712-1-3 (FIGS. 1C and 2).

The H. influenzae PAK 12085 library was plated on LE392 cells on NZCYM plates using 0.7% agarose in NZCYM as overlay. Plaques were lifted onto nitrocellulose and filters were processed and probed with the digoxigenin-labelled 5'pBHIT2 probe (FIG. 2). Putative plaques were plated and subjected to a second round of screening using the same procedures. Phage DNA was prepared from 500 ml cultures by standard techniques, the DNA insert was excised by digestion with Sal I, and cloned into pUC to generate clone JB-1042-7-6 (FIGS. 1D and 2).

The H. influenzae SB33 library was plated on LE392 cells on NZCYM plates using 0.7% agarose in NZCYM as overlay. Plaques were lifted onto nitrocellulose and filters were processed and probed with the digoxigenin-labelled 5'pBHIT2 probe (FIG. 2). Putative plaques were plated and subjected to a second round of screening using the same procedures. Phage DNA was prepared from 500 ml cultures by standard techniques, the DNA insert was excised by digestion with Sal I, and cloned into pUC to generate clone JB-1031-2-9 (FIG. 2).

Example 4

This Example illustrates the sequencing of the Tbp1 and Tbp2 genes of the TfR operon.

Plasmid DNA from clones PBHIT 1, pBHIT 2, S-4368-3-3, JB-901-5-3, DS-712-1-3, JB-1042-7-6 and JB-1031-2-9 was prepared using standard techniques. Oligonucleotide sequencing primers of 17-25 bases in length were synthesized on the ABI model 380B DNA Synthesizer and purified by chromatography using OPC cartridges obtained from Applied Biosystems Inc., and used in accordance with the manufactures recommendations. Samples were sequenced using the ABI model 370A DNA Sequencer and dye terminator chemistry according to manufacturers' protocols. The sequence of the TfR operon from strain DL63 is illustrated in FIG. 3, that of strain Eagan in FIG. 4, that of strain MinnA in FIG. 5, that of PAK 12085 in FIG. 6 and that of SB33 in FIG. 7.

Example 5

This Example illustrates the PCR amplification of the tbp2 genes from non-typable H. influenzae strains SB12, SB29, SB30, and SB32.

Chromosomal DNA from non-typable H. influenzae strains SB12, SB29, SB30, and SB32 was prepared as described aobve. The TfR genes are arranged as an operon with tbp2 followed by tbp1 (see FIGS. 12A (SEQ ID Nos: 116, 117, 118, 119) and 12B (SEQ ID Nos: 121, 122, 123, 124, 125, 126, 127, 128)). Oligonucleotides were synthesized to the 5'-end of the tbp2 and the reverse complement of the 5'-end of the tbpl coding sequences. The primers were: GGATCCATATGAAATCTGT ACCTCTTATCTCTGGT (SEQ ID NO: 120) corresponding to MKSVPLISGS (SEQ ID NO: 147) from the leader sequence of Tbp2 and TCTAGAAGCTTTTTTAGTCATTTTTAGTATTCCAT (SEQ ID NO: 137) which is the reverse complement of the leader sequence MTKK (SEQ ID NO: 138) of Tbp1 and a part of the intergenic sequence (FIGS. 12A and 12B). PCR amplification was performed in buffer containing 10 mM Tris/HCl pH 8.3, 50 mM potassium chloride and 1.5 mM magnesium chloride. Each 100 μl reaction mixture contained 5 ng of chromosomal DNA, 1 μg of each primer, 5 units amplitaq DNA polymerase (Perkin Elmer Cetus) and 0.4 mM dNTPs (Perkin Elmer Cetus). The cycling conditions were 25 cycles of 94° C. for 1.0 min, 45° C. for 2.0 min and 72° C. for 1.5 min. Specific 2 kb fragments were amplified for each sample (FIG. 13). SB33 DNA was used as a positive control (Lane 1). Chromosomal DNA used for amplification of the Tbp2 gene were lane 1, SB33; lane 2, SB12; lane 3, SB29; lane 4, SB30; and lane 5, SB32. The fragments were cloned into the TA cloning vector (Invitrogen) and their nucleotide sequences determined. The nucleic acid sequences of Tbp2 from strains SB12 (SEQ ID NO: 108), SB29 (SEQ ID NO: 110), SB30 (SEQ ID NO: 112) and SB32 (SEQ ID NO: 114) are shown in FIGS. 8, 9, 10 and 11 respectively.

Example 6

This Example illustrates the comparison of the amino acid sequences of transferrin the identification of potentially exposed epitopes of transferrin receptor proteins by secondary structure analysis.

Referring to FIG. 14, there is shown a comparison of the amino acid sequence of Tbp1 from H. influenzae type b Eagan, DL63, non-typable H. influenzae strains PAK 12085 and SB33, N. meningitidis strains B16B6 and M982 (Legrain et al., 1993) and N. gonorrhoeae FA19 (Cornelissen et al., 1992). This analysis revealed regions of Tbp1 which are conserved among all these bacteria.

Referring to FIG. 15, there is shown a comparison of the amino acid sequence of Tbp2 from H. influenzae type b strains Eagan, DL63, non-typable H. influenzae PAK 12085, SB12, SB29, SB30 and SB32, N. meningitidis strains B16B6 and M982, N. gonorrhoeae FA19 and Actinobacillus (Haemophilus) pleuropneumoniae (Gerlach et al., 1992) 205 and 37. This analysis revealed regions of Tbp2 which are conserved among all these bacteria.

Protein secondary structure analyses were performed using the Chou and Fasman algorithms (1978) and hydrophilicity/hydrophobicity plots were performed using the Hopp algorithm (1986). The values were derived from the averages of heptapeptide windows and are plotted at the midpoint of each fragment. FIG. 16A illustrates the predicted secondary structure of Tbp1 from H. influenzae type b Eagan and FIG. 16B illustrates the predicted secondary structure of Tbp2 from H. influenzae type b Eagan. The predicted secondary structures depicted in FIGS. 16A and 16B were arrived at using the procedures described above. However, the inventors have not yet been able to verify that the secondary structure is accurately depicted by these Figures.

Conserved epitopes of Tbp1 and Tbp2 proteins from several different bacteria were identified by sequence alignment as shown in FIGS. 14 and 15 respectively. Some such conserved epitopes include:

    ______________________________________                                         TBP1     DNEVTGLGK          SEQ ID NO:43                                         TBP1 EQVLNIRLTRYDPGI SEQ ID NO:44                                              TBP1 GAINEIEYENVKAVEISKG SEQ ID NO:45                                          TBP1 GALAGSV SEQ ID NO:46                                                      TBP2 LEGGFYGP SEQ ID NO:74                                                     TBP2 CSGGGSFD SEQ ID NO:75                                                     TBP2 YVYSGL SEQ ID NO:76                                                       TBP2 CCSNLSYVKFG SEQ ID NO:77                                                  TBP2 FLIGHRT SEQ ID NO:78                                                      TBP2 EFNVDF SEQ ID NO:79                                                       TBP2 NAFTGTA SEQ ID NO:80                                                      TBP2 VNGAFYG SEQ ID NO:81                                                      TBP2 LEGGYF SEQ ID NO:82                                                       TBP2 VVFGAR SEQ ID NO:83                                                     ______________________________________                                    

Furthermore, in combination with the predicted secondary structures, four conserved exposed epitopes were identified on Tbp1 and two were identified on Tbp2. These are:

    ______________________________________                                         Tbp1  DNEVTGLGK        SEQ ID NO:43                                              Tbp1 EQVLN/DIRDLTRYD SEQ ID NOS: 139 and 140                                   Tbp1 GAINEIEYENVKAVEISK SEQ ID NO:141                                          Tbp1 GI/VYNLF/LNYRYVTWE SEQ ID NOS:142 and 143                                 Tbp2 CS/LGGG(G)SFD SEQ ID NOS: 75, 144 and 145                                 Tbp2 LE/SGGFY/FGP SEQ ID NOS: 74 and 146                                     ______________________________________                                    

Proteins, polypeptides or peptides containing the afore-mentioned conserved amino acid sequences are particularly useful as detecting means in diagnostic embodiments and as immunogens to detect or protect from diseases caused by bacteria that produce transferrin receptor protein. For immunization, the particularly indicated amino acid sequences may be presented to the immune system as proteins or peptides or a live delivery vehicle, such as Salmonella, BCG, adenovirus, poxvirus, vaccinia or poliovirus may be used.

Example 7

This Example illustrates the construction of plasmid JB-1468-29 which expresses Eagan Tbp1 from E. coli.

Plasmids S-4368-3-3 (FIGS. 1B and 2) and JB-911-3-2 (FIG. 17) contain the 5'- and 3'- parts of the Eagan tbp1 gene, respectively. FIG. 17 illustrates the construction scheme for plasmid JB-1468-29. The oligonucleotide sequences used in the construction of JB-1468-29 are shown in FIG. 20, (SEQ ID NOS: 86 and 87). Plasmid JB-1468-29 was introduced into E. coli strain BL21/DE3 by electroporation to generate strain JB-1476-2-1.

JB-1476-2-1 was grown in YT medium and induced with IPTG following standard protocols. For preparation of Tbp1 for immunogenicity and other studies, strain JB-1476-2-1 was grown overnight in NZCYM media containing 3% glucose. A 1:40 inoculum was added to fresh NZCYM media without glucose, and the culture grown to A₅₇₈ =0.3 Lactose was added to 1% and the culture was induced for 4 hours. SDS-PAGE analysis of whole cell lysates of JB-1476-2-1 is shown in FIG. 22. Lane 1, JB-1476-2-1 (T7/Eagan Tbp1) at t_(o) ; lane 2, JB-1476-2-1 at t=4h induction; lane 3, molecular weight markers of 200 kDa, 116 kDa, 97.4 kDa, 66 kDa, 45 kDa and 31 kDa; lane 4, JB-1437-4-1 (T7/Eagan Tbp2) at t_(o) ; lane 5, JB-1437-4-1 at t=4h induction; lane 6, JB-1607-1-1 (T7/SB12 Tbp2) at t_(o) ; lane 7, JB-1607-1-1 at t=4h induction.

Example 8

This Example illustrates the construction of plasmid JB-1424-2-8 which expresses Eagan Tbp2 from E. coli.

Referring to FIG. 18, there is shown plasmid S-4368-3-3 which contains the entire tbp2 gene from H. influenzae type b Eagan. FIG. 18 illustrates plasmid JB-1424-2-8 and FIG. 19 shows the oligonucleotides used. Plasmid JB-1424-2-8 was introduced into E. coli strain BL21/DE3 by electroporation to generate E. coli strain JB-1437-4-1. Upon induction with IPTG or lactose, Tbp2 was expressed by E. coli JB-1437-4-1 as shown in FIG. 22. Lane 1, JB-1476-2-1 (T7/Eagan Tbp1) at t_(o) ; lane 2, JB-1476-2-1 at t=4h induction; lane 3, molecular weight markers of 200 kDa, 116 kDa, 97.4 kDa, 66 kDa, 45 kDa and 31 kDa; lane 4, JB-1437-4-1 (T7/Eagan Tbp2) at t_(o) ; lane 5, JB-1437-4-1 at t=4h induction; lane 6, JB-1607-1-1 (T7/SB12 Tbp2) at t_(o) ; lane 7, JB-1607-1-1 at t=4h induction.

Example 9

This Example illustrates the construction of plasmids which encode a lipoprotein leader sequence before the Tbp2 sequence.

Oligonucleotides used for the construction of plasmids with lipoprotein leader sequences derived from E. coli lpp (SEQ ID NOS: 88 and 89), rlpB (SEQ ID NOS: 90 and 91), and pal (SEQ ID NOS: 92 and 93) preceeding Tbp2 are shown in FIG. 20. Plasmids constructed and corresponding strains generated are illustrated in Table 1 below.

Example 10

This Example illustrates the construction of plasmid JB-1600-1 which expresses SB12 Tbp2 from E. coli.

Plasmid DS-1047-1-2 (FIG. 21) contains the PCR-amplified SB12 tbp2 gene. The tbp2 gene was excised as a Nde I to EcoR I restriction fragment and inserted into the pT7-7 expression vector to generate plasmid JB-1600-1. Electroporation into BL21/DE3 cells yielded E. coli strain JB-1607-1-1 which expresses SB12 Tbp2. Upon induction with IPTG or lactose, SB12 Tbp2 was expressed, as shown in FIG. 22. Lane 1, JB-1476-2-1 (T7/Eagan Tbp1) at t_(o) ; lane 2, JB-1476-2-1 at t=4h induction; lane 3, molecular weight markers of 200 kda, 116 kDa, 97.4 kDa, 66 kDa, 45 kDa and 31 kDa; lane 4, JB-1437-4-1 (T7/Eagan Tbp2) at t_(o) ; lane 5, JB-1437-4-1 at t=4h induction; lane 6, JB-1607-1-1 (T7/SB12 Tbp2) at t_(o) ; lane 7, JB-1607-1-1 at t=4h induction.

Example 11

This Example illustrates the extraction and purification of Tbp1 and Tbp2.

The purification scheme for Tbp1 and Tbp2 is shown in FIG. 23. Both recombinant proteins are expressed as inclusion bodies in E. coli and the purification schemes are identical. Cells from a 500 ml culture, prepared as described in Example 7 for Tbp1 and in Example 8 for Tbp2, were resuspended in 50 ml of 50 mM Tris-HCl, pH 8.0, and disrupted by sonication (3×10 min, 70% duty circle). The extract was centrifuged at 20,000×g for 30 min and the resultant supernatant which contained>95% of the soluble E. coli proteins was discarded.

The remaining pellet (FIG. 23, PPT₁) was further extracted in 50 ml of 50 mM Tris, pH 8.0 containing 0.5% Triton X-100 and 10 mM EDTA. After centrifugation at 20,000×g for 30 min, the supernatant containing residual soluble proteins and the majority of the membrane proteins, was discarded. The resultant pellet (FIG. 23, PPT₂) obtained after the above extraction, contained the inclusion bodies. The Tbp1 and Tbp2 proteins were solubilized in 50 mM Tris, pH 8.0, containing 0.1% SDS and 5 mM DTT. After centrifugation, the resultant supernatant was further purified on a Superdex 200 gel filtration column equilibrated in 50 mM Tris, pH 8.0, containing 0.1% SDS and 5 mM DTT. The fractions were analysed by SDS PAGE and those containing purified Tbp1 or Tbp2 were dialysed overnight at 4° C. against 50 mM Tris, pH 8.0 and then centrifuged at 20,000×g for 30 min. The protein remained soluble under these conditions and the purified Tbp1 and Tbp2 were stored at -20° C.

The SDS-PAGE analysis of the purification process is shown in FIG. 24. Lanes 1, prestained molecular weight protein markers (106, 80, 49.5, 32.5, 27.5, 18.5 kDa); lanes 2, E.coli whole cell lysates; lanes 3, solubilized inclusion bodies; lanes 4, purified Tbp1 or Tbp2.

Example 12

This Example illustrates immunogenicity studies of recombinant Tbp1 and Tbp2 in mice.

Groups of five Balb/c mice were injected subcutaneously (s.c.) on days 1, 29 and 43 with purified rTbp1 or rTbp2 (1 μg to 10 μg), prepared as described in Example 11, in the presence of A1PO₄ (1.5 mg per dose). Blood samples were taken on days 14, 28, 42 and 56 for analysis of the anti-rTbp1 and anti-rTbp2 antibody titers by EIA. The results of the immunogenicity studies are illustrated in FIG. 25.

Example 13

This Example illustrates the development of EIAs for determination of anti-rTbp1 and anti-rTbp2 antibodies in mouse sera.

Anti-rTbp1 and anti-rTbp2 antibody titers were determined essentially as described by Panezutti et al. (1993). Microtiter wells were coated with 0.5 μg of rTbp1 or rTbp2, prepared as described in Example 11, for 16 h at room temperature, then blocked with 0.1% (w/v) BSA in PBS. The sera were serially diluted, added to the wells, then incubated for one hour at room temperature. Affinity-purified F(ab')₂ fragments of goat anti-mouse IgG (Fc specific) antibody conjugated to horseradish peroxidase were used as second antibody. The reactions were developed using tetramethylbenzidine (TMB/H₂ O₂) and the absorbance was measured at 450 nm (using 540 nm as a reference wavelength) in a Flow Multiskan MCC microplate reader. The reactive titer of an antiserum was defined as the reciprocal of the dilution consistently showing a two-fold increase in absorbance over that obtained with the pre-immune serum sample.

Example 14

This Example illustrates the cross-reactivity of anti-Tbp1 antisera, produced by immunization with recombinant Eagan Tbp1, with various strains of H. influenzae.

Whole cell lysates of H. influenzae strains grown in EHI media supplemented with and and heme (Harkness et al., 1992) ±EDDA were separated by SDS PAGE gel, transferred to nitrocellulose membrane, and probed with guinea pig anti-Tbp1 antisera raised to purified recombinant Eagan Tbp1 (FIG. 26). Lane 1, BL21/DE3; lane 2, SB12-EDDA; lane 3, SB12 +EDDA; lane 4, SB29 -EDDA; lane 5, SB29 +EDDA; lane 6, SB33 -EDDA; lane 7, SB33 +EDDA; lane 8, Eagan -EDDA; lane 9, Eagan +EDDA; lane 10, B. catarrhalis 4223 -EDDA; lane 11, B. catarrhalis 4223 +EDDA; lane 12, N. meningitidis 608 -EDDA; lane 13, N. meningitidis 608 +EDDA; lane 14, induced JB-1476-2-l expressing recombinant Eagan Tbp1; lane 5, molecular weight markers. Specific˜95 kDa bands reacted with the anti-Tbp1 antisera in lanes 3, 4, 5, 7, 8 and 9, corresponding H. influenzae strains SB12, SB29, SB33 and Eagan; ˜110 kDa bands in lanes 10 and 11, corresponding B. catarrhalis strain 4223; and ˜80 kDa bands in lanes 12 and 13, corresponding to N. meningitidis 608.

Example 15

This Example illustrates the cross-reactivity of anti-Tbp2 antisera, produced by immunization with recombinant Eagan Tbp2, with various strains of H. influenzae.

Whole cell lysates of H. influenzae strains grown in BHI media supplemented with NAD and heme (Harkness et al., 1992) ±EDDA were separated on an SDS PAGE gel, transferred to nitrocellulose membrane, and probed with guinea pig anti-Tbp2 antisera raised to purified recombinant Eagan Tbp2 (FIG. 27). Lane 1, molecular weight markers; lane 2, induced JB-1437-4-1 expressing recombinant Eagan Tbp2; lane 3, SB12-EDDA; lane 4, SB12 +EDDA; lane 5, SB29 -EDDA; lane 6, SB29 +EDDA; lane 7, SB30 -EDDA; lane 8, SB30 +EDDA; lane 9, SB32 -EDDA; lane 10, SB33-EDDA; lane 11, SB33 +EDDA; lane 12, PAK -EDDA; lane 13, PAK +EDDA; lane 14, Eagan -EDDA; lane 15, Eagan +EDDA. Specific bands of about 60-70 kDa were reactive with the anti-Tbp2 antisera in lanes 3, 6, 7, 8, 13, 14 and 15, corresponding to Haemophilus strains SB12, SB29, SB30, PAK and Eagan.

Example 16

This Example illustrates the synthesis of synthetic peptides corresponding to conserved regions in Tbp2 and Tbp1.

The deduced amino acid sequences of Tbp1 and Tbp2 were compared as shown in FIGS. 14 and 15 respectively. This comparison identified regions of amino acid sequence conservation within the transferrin receptor described above and, as shown in Tables 2 and 3, peptides were synthesized containing a portion of the transferrin receptor. Such synthesis may be effected by expression in a suitable host of recombinant vectors containing nucleic acid encoding said peptides or by standard peptide synthesis.

Briefly, peptides were synthesized using an ABI 430A peptide synthesizer and optimized t-Boc chemistry using the conditions recommended by the manufacturer, and peptides were cleaved from the resin using hydrofluoric acid (HF). The peptides were purified by reverse-phase high performance liquid chromatography (RP-HPLC) on a Vydac C4 semi-preparative column (1×30 cm) using a 15 to 55% acetonitrile gradient in 0.1.% trifluoryl acetic acid (TFA) developed over 40 minutes at a flow rate of 2 ml/minute. All synthetic peptides used in biochemical and immunological studies were >95% pure as judged by analytical HPLC. Amino acid composition analyses were performed on a Waters Pico-Tag system and were in good agreement with the theoretical compositions.

Example 17

This Example illustrates the immunogenicity of synthetic peptides in test animals.

Guinea pigs were immunized intramuscularly with 100 μg of peptide, prepared as described in Example 16, emulsified in Freund's complete adjuvant on day 0 followed by boosters on days +14 and +28 using the same amount of peptide emulsified in Freund's incomplete adjuvant. Sera samples were obtained on day 42+and antibody titers determined by enzyme-linked immunosorbent assay (ELISA). Briefly, microtiter wells (Nunc-Immunoplate, Nunc, Denmark) were coated with 500 ng of any one particular peptide in 50 μL of coating buffer (15 mM Na₂ CO₃, 35 mM NaHCO₃, pH 9.6) for 16 hours at room temperature. The plates were then blocked with 0.1% (w/v) BSA in phosphate buffer saline (PBS) for 30 minutes at room temperature. The antisera were serially diluted, added to the wells and incubated for 1 hour at room temperature. After removal of the antisera, the plates were washed five times with PBS containing 0.1% (w/v) Tween-20 and 0.1% (w/v) BSA. F(ab')₂ from goat anti-guinea pig IgG antibodies conjugated to horseradish peroxidase (Jackson ImmunoResearch Labs Inc., Pa.) were diluted (1/8,000) with washing buffer, and added onto the microtiter plates. After 1 hour of incubation at room temperature, the plates were washed five times with the washing buffer. The plates were developed using the substrate tetramethylbenzidine (TMB) in H₂ O₂ (ADI, Toronto), the reaction was stopped with 1N H₂ SO₄ and the optical density was measured at 450 nm using a Titretek Multiskan II (Flow Labs., Va.). Two irrelevant peptides of 32 amino acid residues were included as negative controls in these ELISAs. Assays were performed in triplicate, and the reactive titer of each antiserum was defined as the dilution consistently showing a 2-fold increase in absorbance value over those obtained from the negative controls. The antisera raised in guinea pigs were monospecific for the peptide used for immunization. The titers of the sera obtained following immunization are shown in Table 4.

Peptides of the present invention comprise single copies of any of those shown in Tables 2 and 3 or peptides containing multiple copies of analogs thereof. A peptide may further comprise multiples of different peptides selected from those shown in Tables 2 and 3 or analogs thereof and include suitable carrier molecules. It is preferred that the peptides from conserved regions be used to develop antibodies because an immuno- or other type of binding assay can then be used to detect several species of Haemophilus. Tables 2 and 3 therefore set out several other conserved regions of transferrin receptor to identify other peptides which would be useful in diagnosis, immunization and medical treatment.

Example 18

This Example describes the ability of antiserum raised against peptides corresponding to conserved portions of transferrin receptor to recognize the transferrin receptor of Branhamella catarrhalis.

Guinea pigs were immunized with peptide, corresponding to conserved portions of transferrin receptor, and antisera obtained are described in Example 17. A whole-cell extract of Branhamella catarrhalis was immunoblotted with the peptide-specific antiserum which specifically recognized the transferrin receptor from this bacterium. Anti-peptide antiserum from a guinea pig immunized with the Tbp2 N-terminal peptide and peptide TBP2-25 specifically recognized Tbp2 protein from Branhamella catarrhalis and recombinant Tbp2 expressed by plasmid clone pBHIT2 in E. coli. Clone pBHIT2 expresses a truncated version of Tbp2 starting at amino acid 80. (i.e. NKKFYSG SEQ ID NO: 105). Therefore, the Tbp2 protein from pBHIT2 can only be recognized by antibodies raised against the second epitope LEGGFYGP (TBP2-25). This analysis shows that peptides corresponding to conserved sequences between transferrin receptor are useful in detecting most, if not all, bacteria that produce transferrin receptor and as components in immunogenic compositions, including vaccines to produce an immune response against transferrin receptor and protect against diseases caused by such bacteria.

The sera from these rabbits were tested by ELISA against a peptide incorporating the sequence LEGGFYGP (SEQ ID NO:74) or against H. influenzae strain DL63, Tbp2. ELISA plates were coated with the peptide or the protein then blocked with 5% skim milk. Serial two-fold dilutions of sera in phosphate buffered saline, 0.05% tween-20, and 1% dried milk were incubated on the plates for two hours at 37° C., following which the plates were washed five times in phosphate buffered saline with 0.05% tween-20. Washed plates were probed with a horse-radish peroxidase (HRPO)-conjugated donkey anti-rabbit IgG for 30 minutes at room temperature, then washed five times in phosphate buffered saline with 0.05% tween-20. HRPO-substrate was added to all wells for 30 minutes at room temperature in the dark, then color developemnt was halted by the addition of 50 ul 1M sulphuric acid. Color was measured by determining absorbance at 450 nm.

Example 19

This Example illustrates the generation of H. influenzae strains that do not produce transferrin receptor.

A 2.55 Eco RI fragment of the insert from pBHIT1 was subcloned into the Eco RI site of pUC4K, resulting in removal of the Tn903 kanamycin resistance (kan) cassette from this vector (pUHITI; FIG. 28). This subcloning step facilitated the subsequent insertion of either a HincII or PstI pUC4K fragment containing the kan cassette into the Hind III or Pst I sites of pUHIT1 as both are unique sites in this construction to produce pUHIT1KFH and pUHIT1KFP, FIG. 28. Following digestion with Eco RI to remove the interrupted gene sequences, the constructs were introduced into the H. influenzae wild type genome by transformation using M-IV media as described previously (Barcak et al., 1991) and transformants were selected on BHINH agar containing 20 μg/ml kanamycin.

Example 20

This Example illustrates the construction of polioviruses expressing an epitope of a transferrin receptor.

A cDNA clone of bases 1175 to 2956 of the poliovirus type 1, Mahoney strain (PV1-M) genome was cut with restriction enzymes Sau I and Hind III. These enzymes excise a fragment containing bases 2754 to 2786, which encodes PV1-M amino acids 1094 to 1102, as shown in FIG. 29. In this application, we use the four-digit code for poliovirus amino-acids; for example, 1095 is amino acid 95 of capsid protein VP1. New hybrid cDNA clones encoding both poliovirus and transferrin receptor amino-acid sequences were constructed by replacing the excised fragment with synthetic oligonucleotides coding for amino acids from H. influenzae Tbp2. The new hybrid cDNA clones were cut with restriction enzymes Nhe I and SnaB I, which excise a hybrid fragment, including the transferrin receptor DNA sequences, from poliovirus base 2471 to 2956. A cDNA clone, for example pT7XLD or pT7CMCB, of the entire genome of PV1-M was cut with Nhe I and SnaBI to excise a fragment from poliovirus base 2471 to 2956. This was then replaced with a hybrid fragment including the transferrin receptor DNA sequences to produce a hybrid cDNA clone of the genome of PV1-M with bases 2754 to 2786 replaced by bases encoding a hybrid BC loop including transferrin receptor amino acids, as shown in FIG. 29.

The plasmid pT7XLD and clones derived from pT7XLD, such as pT7C.MCB, contain a promoter sequence for the enzyme T7 RNA polymerase at the 5' end of the PV1-M cDNA. RNA transcripts of the PV1-M cDNA, including any bases encoding transferrin receptor amino acids, were prepared using T7 RNA polymerase as described by van der Werf et al. Transfection of Vero cells with these RNA transcripts produced four viable hybrid viruses, designated PV1TBP2A, PV1TBP2B, PV1TBP2C. and PV1TBP2D. Transfection with transcripts of pT7C.MCB yielded a transfection-derived wild-type poliovirus designated PV1XLD (FIG. 29).

The antigenic characteristics of PV1TBP2A, PV1TBP2B, PV1TBP2C. and PV1TBP2D are shown in Table 5. All were neutralized by guinea-pig antisera raised against a peptide incorporating the sequence LEGGFYGP (SEQ ID NO: 74), indicating that the viruses expressed this sequence in an antigenically recognisable form. To produce the antisera female guinea pigs were immunized IM with a 500 ul volume containing 200 ug peptide formulated in aluminum phosphate (3 mg/ml). Animals were immunized on days 1, 14, 28 and 42 and bled on days 0, 28, 42 and 56. Sera were from the day 56 bleed. PV1TBP2A and PV1TBP2B were also neutralized by rabbit antisera raised against H. influenzae strain DL63 Tbp2, indicating that at least these two viruses expressed the sequence in a form recognisable to antibodies raised against the protein. All viruses were neutralisable by anti-PV1 sera, indicating that the changes in polio neutralization antigenic site I had not significantly affected other antigenic sites on the viruses.

Example 21

This Example illustrates the use of poliovirus hybrids to induce high titer antisera against Tbp2.

Rabbits were inoculated with CsCl-purified PV1TBP2A (rabbits #40, 41, 42). Note that, although the viruses used were live, poliovirus does not replicate in rabbits and that any response observed is effectively the response to an inactivated antigen. On day 1, rabbits were inoculated with 1 ug of virus in Freund's complete adjuvant subcutaneously on the back, and, on day 14, the rabbits were boosted with 1 ug of virus in Freund's incomplete adjuvant inoculated subcutaneously on the back. The rabbits were bled on day 0 (prebleed) and on day 27. The dose of virus per inoculation was 2.5×10⁸ pfu, which was determined from A₂₆₀ values to be approximately 3.0×10¹¹ virions. This equivalent to 0.5 pmol of virus or 30 pmol of the LEGGFYG (SEQ ID NO: 74) epitope, since each virion expresses 60 copies of the epitope.

SUMMARY OF THE DISCLOSURE

In summary of this disclosure, the present invention provides purified and isolated DNA molecules containing transferrin receptor genes, the sequences of these transferrin receptor genes and the derived amino acid sequences thereof. The invention also provides peptides corresponding to portions of the transferrin receptor. The genes, DNA sequences, recombinant proteins and peptides are useful for diagnosis, immunization and the generation of diagnostic and immunological reagents. Vaccines based upon expressed recombinant Tbp1 and/or Tbp2, portions thereof, or peptides derived from the provided sequences can be prepared for prevention of diseases caused by bacterial pathogens that produce transferrin receptor. Modifications are possible within the scope of this invention.

                  TABLE 1                                                          ______________________________________                                         leader    1st residue                                                                               plasmid     strain                                        ______________________________________                                         E. coli lpp                                                                              Cys        JB-1360-1R-10                                                                              JB-1407-1-1                                     E. coli lpp Ser JB-1366-1R-7 JB-1407-3-1                                       E. coli pal Cys JB-1360-3-10 JB-1407-2-1                                       E. coli pal Ser JB-1366-3R-5JB-1407-4-4                                        E. coli rlpB Cys JB-1399-1 JB-1437-1-1                                         E. coli rlpB Ser JB-1378-7 JB-1407-5-1                                       ______________________________________                                    

                                      TABLE 2                                      __________________________________________________________________________     PREDICTED ANTIGENIC Tbp1 PEPTIDES                                              PEPTIDE                                                                             RESIDUES.sup.1                                                                       SEQUENCES              SEQ ID NO:                                   __________________________________________________________________________     TBP1-N                                                                               1-36 AETQSIKDTKEAISSEVDTQSTEDSELETISVTAEK                                                                  13                                             TBP1-2   31-66 SVTAEKVRDRKDNEVTGLGKIIKTSESISREQVLNI 14                         TBP1-3   59-94 SREQVLNIRDLTRYDPGISVVEQGRGASSGYSIRGM 15                         TBP1-4    88-123 GYSIRGMDRNRVALLVDGLPQTQSYVVQSPLVARSG 16                       TBP1-5   117-152 PLVARSGYGTGAINEIEYENVKAVEISKGGSSSEYG 17                       TBP1-6   147-182 SSSEYGNGALAGSVTFQSKSAADILEGDKSWGIQTK 18                       TBP1-7   179-214 GIQTKNAYSSKNKGFTHSLAVAGKQGGFEGVAIYTH 19                       TBP1-8   208-243 GVAIYTHRNSIETQVHKDALKGVQSYDRFIATTEDQ 20                       TBP1-9   236-271 IATTEDQSAYFVMQDECLDGYDKCKTSPKRPATLST 21                       TBP1-10 266-301 PATLSTQRETVSVSDYTGANRIKPNPMKYESQSWFL 22                        TBP1-11 293-328 YESQSWFLRGGYHFSEQHYIGGIFEFTQQKFDIRDM 23                        TBP1-12 322-357 KFDIRDMTFPAYLRPTEDKDLQSRPFYPKQDYGAYQ 24                        TBP1-13 352-387 DYGAYQHIGDGRGVKYASGLYFDEHHRKQRVGIEYI 25                        TBP1-14 383-418 GIEYIYENKNKAGIIDKAVLSANQQNIILDSYMRHT 26                        TBP1-15 412-447 DSYMRHTHCSLYPNPSKNCRPTLDKPYSYYHSDRNV 27                        TBP1-16 443-478 SDRNVYKEKHNMLQLNLEKKIQQNWLTHQIAFNLGF 28                        TBP1-17 469-504 THQIAFNLGFDDFTSALQHKDYLTRRVIATASSISE 29                        TBP1-18 498-534 TASSISEKRGEARRNGLQSSPYLYPTPKAELVGGDLC 30                       TBP1-19 528-563 LVGGDLCNYQGKSSNYSDCKVRLIKGKNYYFAARNN 31                        TBP1-20 558-593 FAARNNMALGKYVDLGLGMRYDVSRTKANESTISVG 32                        TBP1-21 588-623 STISVGKFKNFSWNTGIVIKPTEWLDLSYRLSTGFR 33                        TBP1-22 618-653 LSTGFRNPSFAEMYGWRYGGKDTDVYIGKFKPETSR 34                        TBP1-23 648-683 KPETSRNQEFGLALKGDFGNIEISHFSNAYRNLIAF 35                        TBP1-24 677-712 YRNLIAFAEELSKNGTTGKGNYGYHNAQNAKLVGVN 36                        TBP1-25 706-741 AKLVGVNITAQLDFNGLWKRIPYGWYATFAYNRVKV 37                        TBP1-26 735-770 AYNRVKVKDQKINAGLASVSSYLFDAIQPSRYIIGL 38                        TBP1-27 764-799 SRYIIGLDYDHPSNTWGIKTMFTQSKAKSQNELLGK 39                        TBP1-28 794-829 NELLGKRALGNNSRNVKSTRKLTRAWHILDVSGYYM 40                        TBP1-29 825-854 SGYYMVNRSILFRLGVYNLLNYRYVTWEAV 41                              TBP1-30 843-865 LLNYRYVTWEAVRQTAQGAEFDI 42                                     TBP1-31 42-50 DNEVTGLGK 43                                                     TBP1-32 61-76 EQVLNIRDLTRYDPGI 44                                              TBP1-33 61-95 EQVLNIRDLTRYDPGISVVEQGRGASSGYSIRGMD 45                           TBP1-34 128-146 GAINEIEYENVKAVEISKG 46                                         TBP1-35 155-161 GALAGSV 47                                                     TBP1-1  1-14 AETQSIKDTKEAISC.sup.2 48                                        __________________________________________________________________________      .sup.1 Residue number from the sequence of Tbp1 of H. influenzae type b        strain Eagan (as shown in FIG. 8).                                             .sup.2 Cysteine added to facilitate coupling to a carrier protein, for         example KLH.                                                             

                                      TABLE 3                                      __________________________________________________________________________     PREDICTED CONSERVED ANTIGENIC Tbp2 PEPTIDES                                    PEPTIDE                                                                             RESIDUES.sup.1                                                                       SEQUENCES              SEQ ID NO:                                   __________________________________________________________________________     TBP2-1                                                                              18-31 CSGGGSFDVDNVSN         49                                             TBP2-2  231-261   LEGGFYGPKGEELGFRFLAGDKKVFGVFSAK 50                           TBP2-3 358-380    TVGKKTYQVEACCSNLSYVKFGM 51                                   TBP2-4 527-549    ATVKGAFYGPKASELGGYFTYNG 52                                   TBP2-5  1-36   MKLAALNLFDRNKPSLLNEDSYMIFSSRSTIEEDV 53                          TBP2-6 29-64      STIEEDVKNDNQNGEHPIDSIVDPRAPNSNENRHG 54                       TBP2-7 57-92      SNENRHGQKYVYSGLYYIQSWSLRDLPNKKFYSGY 55                       TBP2-8  85-120 KKFYSGYYGYAYYFGNTTASALPVGGVATYKGTWS 56                          TBP2-9 113-148    TYKGTWSFITAAENGKNYELLRNSGGGQAYSRRSA 57                       TBP2-10 141-176   AYSRRSATPEDIDLDRKTGLTSEFTVNFGTKKLTG 58                       TBP2-11 169-204   GTKKLTGGLYYNLRETDANKSQNRTHKLYDLEADV 59                       TBP2-12 197-232   YDLEADVHSNRFRGKVKPTKKESSEEHPFTSEGTL 60                       TBP2-13 225-260   FTSEGTLEGGFYGPEGQELGGKFLAHDKKVLGVFS 61                       TBP2-14 253-288   KVLGVFSAKEQQETSENKKLPKETLIDGKLTTFKT 62                       TBP2-15 281-316   KLTTFKTTNATANATTDATTSTTASTKTDTTTNAT 63                       TBP2-16 309-344 DTTTNATANTENFTTKDIPSLGEADYLLIDNYPVP 64                         TBP2-17 337-372 IDNYPVPLFPESGDFISSKHHTVGKKTYQVEACCS 65                         TBP2-M 360-406  CSNLSYVKFGMYYEAPPKEEEKEKEKDKDKEKEKQA 66                        TBP2-19 393-428 KEKDKDKEKEKQATTSIKTYYQFLLGLRTPSSEIP 67                         TBP2-20 421-456 TPSSEIPKEGSAKYHGNWFGYISDGETSYSASGDK 68                         TBP2-21 449-484 YSASGDKERSKNAVAEFNVNFAEKTLTGELKRHDT 69                         TBP2-22 477-512 ELKRHDTQNPVFKINATFQSGKNDFTGTATAKDLA 70                         TBP2-23 505-540 ATAKDLAIDGKNTQGTSKVNFTATVNGAFYGPHAT 71                         TBP2-24 533-559 FYGPHATELGGYFTYNGNNPTDKNSS 72                                  TBP2-C 553-581  CPTDKNSSSNSEKARAAVVFGAKKQQVETTK 73                             TBP2-25 231-238 LEGGFYGP 74                                                    TBP2-26 18-25 CSGGGSFD 75                                                      TBP2-27 130-134 YVYSGL 76                                                      TBP2-28 345-355 CCSNLSYVKFG 77                                                 TBP2-29 401-407 FLLGHRT 78                                                     TBP2-30 450-456 EFNVDF 79                                                      TBP2-31 485-491 NAFTGTA 80                                                     TBP2-32 516-522 VNGAFYG 81                                                     TBP2-33 527-532 ELGGYT 82                                                      TBP2-34 562-566 VVFGAR 83                                                      TBP2-35 562-568 VVFGAK 84                                                      TBP2-36 231-238 LEGGFYG 85                                                   __________________________________________________________________________      .sup.1 Residue number from the sequence of Tbp2 of H. influenzea type B        Eagan strain (as show in FIG. 9).                                        

                                      TABLE 4                                      __________________________________________________________________________     Guinea pig antibody responses to Tbp1 and Tbp 2 peptides                       PEPTIDE                                                                             SEQ ID                                                                              SEQUENCES               TITRE                                        __________________________________________________________________________     TBP1-N                                                                              13   AETQSIKDTKEAISSEVDTQSTEDSELETISVTAEK                                                                   500                                            TBP1-M 30 TASSISEKRGEARRNGLQSSPYLYPTPKAELVGGDLC 1562500                        TBP1-1 48 AETQSIKDTKEAISC <100                                                 TBP2-1 49 CSGGGSFDVDNVSN 2500                                                  TBP2-2 50 LEGGFYGPKGEELGFRFLAGDKKVFGVFSAK 12500                                TBP2-3 51 TVGKKTYQVEACCSNLSYVKFGM 62500                                        TBP2-4 52 ATVKGAFYGPKASELGGYFTYNG <100                                         TBP2-M 66 CSNLSYVKFGMYYEAPPKEEEKEKEKDKDKEKEKQA 62500                           TBP2-C 73 CPTDKNSSSNSEKARAAVVFGAKKQQVETTK 312500                             __________________________________________________________________________

                                      TABLE 5                                      __________________________________________________________________________     Neutralizing activity of anti-Tbp2 and anti-peptide sera                         against polio/Tbp2 hybrid viruses                                                     Neutralizing Titre v. Virus.sup.b                                     Sera.sup.a                                                                              PV1TBP2A                                                                             PV1TBP2B                                                                             PV1TBP2C                                                                             PV1TBP2D                                                                             PV1XLD                                        __________________________________________________________________________     Rb @PV1  >40,9600                                                                             25,844                                                                               20,480                                                                               16,763                                                                               >40,960                                         Rb 516 D0                    <4          <4          <4          <4                                             <4                                            Rb 516 D42                   40            20            <4                                                   <4    <4                                        GP561, 562 D0 pool           <4            <4            <4      <4                                           <4                                              GP 561 D56                  >2048         >2048     >2048         1164                                          <4                                            GP 562 D56                  >2048         >2048          25          10                                           <4                                          GP558, 559, 560              <4            <4            <4       <4                                          <4                                              D56 pool                                                                     __________________________________________________________________________      .sup.a Rb @PV1 is pool of rabbit immune sera raised against PV1XLD. Rabbi      516 was immunised with three successive 3 μg dses of recombinant H.         influenzae DL63 transferrin binding protein 2 on days 1, 14 and 28. Serum      was collected on days 0 (D0) and 42 (D42). Guineapigs were immunized with      four successive doses of 200 μg of peptide on days 1, 14, 28 and 42.        Sera were collected on day 0 (D0) and day 56 (D56). GuineaPigs 561 and 56      received a peptide containing the sequence LEGGFYGP  # (SEQ ID NO:74).         Guineapigs 558, 559 and 556 received a control peptide with an unrelated       sequence.                                                                      .sup.b Titre is the inverse dilution of serum giving a 50% endpoint in a       virus neutralization assay versus 100 TCID.sub.50 of virus.              

                  TABLE 6                                                          ______________________________________                                         Peptide-specific IgG titres of rabbits imminised with                            PVITBP2A or PV1TBP2B                                                                       PEPTIDE-SPECIFIC IgG TITRES.sup.a                                RABBIT (ANTIGEN)                                                                             PREBLEED        DAY 27                                           ______________________________________                                         40 (PV1TBP2A) <20             640                                                41 (PV1TBP2A) <20 640                                                          42 (PV1TBP2A) <20 2560                                                         43 (PV1TBP2B) <20 160                                                          44 (PV1TBP2B) <20 1280                                                         45 (PV1TBP2B) <20 1280                                                         10 (PV1 Mahoney)  <20.sup.b                                                    11 (PV1 Mahoney)  <20                                                        ______________________________________                                          .sup.a Titres are the reciprocal of the greatest dilution of sera giving       and A.sub.450 of at least twice the background value. The background valu      was the mean A.sub.450 of wells assayed in the absence of rabbit Sera.         .sup.b Titres for rabbits 10 and 11 refer to sera taken on day 42 after        three immunisations with PV1 Mahoney. Rabbits 10 and 11 were immunised as      rabbits 40 to 45, except that an additional booster dose was administered      on day 28.                                                               

LIST OF REFERENCES

Barcak et al., (1991) Methods Enzymol. 204: 321-342.

Berkowitz et al., (1987) J. Pediatr. 110:509.

Black et al., (1991) Pediatr. Infect. Dis. J. 10:97.

Bluestone, N. (1982) Engl. J. Med. 306:1399.

Chang et al., (1978) Nature 375:615.

Chou, et al., (1978). Annual Reviews of Biochemistry 47, 251-276.

Claesson et al., (1989) J. Pediatr. 114:97.

Cornelissen et al., (1992) J. Bacteriol. 174:5788

Danve, et al., (1993). Vaccine 11, 1214-1220.

Deres et al., (1989) Nature 342:651.

Gerlach, et al., (1992) Infect. Immun. 608:325

Goeddel et al., (1979) Nature 281:544.

Goeddel et al., (1980) Nucl. Acids Res. 8:4057

Harkness et al., (1992) J. Bacteriol. 174:2425.

Holland et al., (1992) Infect. Immun. 60:2986.

Hopp, T. P. (1986) Journal of Immunological Methods 88, 1-18.

Itakura et al., (1977) Science 198:1056.

Jarosik et al., (1994). Infection and Immunity 62, 2470-2477.

Legrain et al., (1993). Gene 130:73

Lockhoff et al., (1991) Chem. Int. Ed. Engl. 30:1611.

Mickelsen and Sparling, (1981) Infect. Immun. 33:555.

Morton et al., (1993) Infection and Immunity 61, 4033-4037.

Murdin et al., (1992) J. Gen. Viral 73: 607.

Murdin et al., (1991) Microbial Pathogenesis 10:27.

Nixon-George et al., (1990) J. Immunol. 14:4798.

Ogunnariwo, and Schryvers, (1992) Avian Dis. 36:655.

O'Hagan (1992) Clin Pharmokinet. 22:1.

Panezutti et al., (1993) Infection and Immunity 61, 1867-1872.

Roosi-Campos et al., (1992) Vaccine 10, 512-518.

Schryvers, (1988) Molec. Microbiol. 2:467.

Schryvers and Lee, (1989) Can. J. Microbiol. 35:409.

Schryvers and Gray-Owen, (1992) J. Infect. Dis. 165 suppl 1:S103.

Schryvers (1989) Med. Microbiol. 29:121.

Short et al., (1988) Nucl. Acids Res. 16:7583.

Ulmer et al., (1993) Curr. Opinion Invest. Drugs. 2 (9): 983-989.

Van der Werf et al., (1986) Proc. Natl. Acad. Sci. 83: 2330.

Weismuller et al., (1989) Vaccine 8:29.

Wilton et al., (1993) FEMS Microbiology Letters 107, 59-66.

U.S. Pat. No. 4,855,283

U.S. Pat. No. 4,258,029

U.S. Pat. No. 4,496,538

U.S. Pat. No. 4,599,230

U.S. Pat. No. 4,599,231

U.S. Pat. No. 4,601,903

U.S. Pat. No. 5,141,743

U.S. Pat. No. 4,596,792

U.S. Pat. No. 4,952,496

U.S. Pat. No. 5,194,254

WO 92/17167

    __________________________________________________________________________     #             SEQUENCE LISTING                                                    - -  - - (1) GENERAL INFORMATION:                                              - -    (iii) NUMBER OF SEQUENCES: 147                                          - -  - - (2) INFORMATION FOR SEQ ID NO:1:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 4699 base - #pairs                                                 (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: double                                                       (D) TOPOLOGY: linear                                                  - -     (ix) FEATURE:                                                                   (A) NAME/KEY: CDS                                                              (B) LOCATION: join(10..194 - #0, 1957..4696)                          - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:1:                                - - TATAACTCA ATG AAA TCT GTA CCT CTT ATC TCT GGT - # GGA CTT TCC TTT              48                                                                                 Met Lys Ser Val Pro - #Leu Ile Ser Gly Gly Leu Ser Phe                           1      - #         5         - #         10                         - - TTA CTA AGT GCT TGT AGC GGA GGG GGG TCT TT - #T GAT GTA GAT AAC GTC            96                                                                        Leu Leu Ser Ala Cys Ser Gly Gly Gly Ser Ph - #e Asp Val Asp Asn Val                 15             - #     20             - #     25                           - - TCT AAT ACC CCC TCT TCT AAA CCA CGT TAT CA - #A GAC GAT ACT TCA AGT           144                                                                        Ser Asn Thr Pro Ser Ser Lys Pro Arg Tyr Gl - #n Asp Asp Thr Ser Ser             30                 - # 35                 - # 40                 - # 45        - - TCA AGA ACA AAA TCT AAA TTG GAA AAG TTG TC - #C ATT CCT TCT TTA GGG           192                                                                        Ser Arg Thr Lys Ser Lys Leu Glu Lys Leu Se - #r Ile Pro Ser Leu Gly                             50 - #                 55 - #                 60               - - GGA GGG ATG AAG TTA GCG GCT CTG AAT CTT TT - #T GAT AGG AAC AAA CCT           240                                                                        Gly Gly Met Lys Leu Ala Ala Leu Asn Leu Ph - #e Asp Arg Asn Lys Pro                         65     - #             70     - #             75                   - - AGT CTC TTA AAT GAA GAT AGC TAT ATG ATA TT - #T TCC TCA CGT TCT ACG           288                                                                        Ser Leu Leu Asn Glu Asp Ser Tyr Met Ile Ph - #e Ser Ser Arg Ser Thr                     80         - #         85         - #         90                       - - ATT GAA GAG GAT GTT AAA AAT GAC AAT CAA AA - #C GGC GAG CAC CCT ATT           336                                                                        Ile Glu Glu Asp Val Lys Asn Asp Asn Gln As - #n Gly Glu His Pro Ile                 95             - #    100             - #    105                           - - GAC TCA ATA GTC GAT CCT AGA GCA CCA AAT TC - #A AAC GAA AAT CGT CAT           384                                                                        Asp Ser Ile Val Asp Pro Arg Ala Pro Asn Se - #r Asn Glu Asn Arg His            110                 1 - #15                 1 - #20                 1 -       #25                                                                               - - GGA CAA AAA TAT GTA TAT TCA GGG CTT TAT TA - #T ATT CAA TCG TGG         AGT      432                                                                     Gly Gln Lys Tyr Val Tyr Ser Gly Leu Tyr Ty - #r Ile Gln Ser Trp Ser                           130  - #               135  - #               140               - - CTA AGA GAT TTA CCA AAT AAA AAG TTT TAT TC - #A GGT TAC TAT GGA TAT           480                                                                        Leu Arg Asp Leu Pro Asn Lys Lys Phe Tyr Se - #r Gly Tyr Tyr Gly Tyr                        145      - #           150      - #           155                   - - GCG TAT TAC TTT GGC AAT ACA ACT GCC TCT GC - #A TTA CCT GTA GGT GGC           528                                                                        Ala Tyr Tyr Phe Gly Asn Thr Thr Ala Ser Al - #a Leu Pro Val Gly Gly                    160          - #       165          - #       170                       - - GTA GCA ACG TAT AAA GGA ACT TGG AGC TTC AT - #C ACC GCA GCT GAA AAT           576                                                                        Val Ala Thr Tyr Lys Gly Thr Trp Ser Phe Il - #e Thr Ala Ala Glu Asn                175              - #   180              - #   185                           - - GGC AAG AAT TAT GAA TTG TTA AGA AAT TCT GG - #T GGC GGT CAA GCT TAT           624                                                                        Gly Lys Asn Tyr Glu Leu Leu Arg Asn Ser Gl - #y Gly Gly Gln Ala Tyr            190                 1 - #95                 2 - #00                 2 -       #05                                                                               - - TCT CGA CGT AGT GCT ACT CCA GAA GAT ATT GA - #T TTA GAT CGT AAG         ACG      672                                                                     Ser Arg Arg Ser Ala Thr Pro Glu Asp Ile As - #p Leu Asp Arg Lys Thr                           210  - #               215  - #               220               - - GGC TTA ACA AGT GAA TTT ACT GTC AAT TTT GG - #T ACA AAA AAG CTC ACT           720                                                                        Gly Leu Thr Ser Glu Phe Thr Val Asn Phe Gl - #y Thr Lys Lys Leu Thr                        225      - #           230      - #           235                   - - GGA GGA CTT TAT TAT AAT TTA CGT GAA ACA GA - #T GCT AAT AAA TCA CAA           768                                                                        Gly Gly Leu Tyr Tyr Asn Leu Arg Glu Thr As - #p Ala Asn Lys Ser Gln                    240          - #       245          - #       250                       - - AAT AGA ACA CAT AAA CTC TAC GAT CTA GAA GC - #T GAT GTT CAT AGC AAC           816                                                                        Asn Arg Thr His Lys Leu Tyr Asp Leu Glu Al - #a Asp Val His Ser Asn                255              - #   260              - #   265                           - - CGA TTC AGG GGT AAA GTA AAG CCA ACC AAA AA - #A GAG TCT TCT GAA GAA           864                                                                        Arg Phe Arg Gly Lys Val Lys Pro Thr Lys Ly - #s Glu Ser Ser Glu Glu            270                 2 - #75                 2 - #80                 2 -       #85                                                                               - - CAT CCC TTT ACC AGC GAG GGA ACA TTA GAA GG - #T GGT TTT TAC GGG         CCT      912                                                                     His Pro Phe Thr Ser Glu Gly Thr Leu Glu Gl - #y Gly Phe Tyr Gly Pro                           290  - #               295  - #               300               - - GAG GGT CAA GAA TTA GGA GGA AAG TTT TTA GC - #T CAC GAC AAA AAA GTT           960                                                                        Glu Gly Gln Glu Leu Gly Gly Lys Phe Leu Al - #a His Asp Lys Lys Val                        305      - #           310      - #           315                   - - TTG GGG GTA TTT AGT GCC AAA GAA CAG CAA GA - #A ACG TCA GAA AAC AAA          1008                                                                        Leu Gly Val Phe Ser Ala Lys Glu Gln Gln Gl - #u Thr Ser Glu Asn Lys                    320          - #       325          - #       330                       - - AAA TTA CCC AAA GAA ACC TTA ATT GAT GGC AA - #G CTA ACT ACT TTT AAA          1056                                                                        Lys Leu Pro Lys Glu Thr Leu Ile Asp Gly Ly - #s Leu Thr Thr Phe Lys                335              - #   340              - #   345                           - - ACA ACC AAT GCA ACA GCC AAT GCA ACA ACC GA - #T GCA ACA ACC AGT ACA          1104                                                                        Thr Thr Asn Ala Thr Ala Asn Ala Thr Thr As - #p Ala Thr Thr Ser Thr            350                 3 - #55                 3 - #60                 3 -       #65                                                                               - - ACA GCC AGT ACA AAA ACC GAT ACA ACA ACC AA - #T GCA ACA GCC AAT         ACA     1152                                                                     Thr Ala Ser Thr Lys Thr Asp Thr Thr Thr As - #n Ala Thr Ala Asn Thr                           370  - #               375  - #               380               - - GAA AAC TTT ACG ACA AAA GAT ATA CCA AGT TT - #G GGT GAA GCT GAT TAT          1200                                                                        Glu Asn Phe Thr Thr Lys Asp Ile Pro Ser Le - #u Gly Glu Ala Asp Tyr                        385      - #           390      - #           395                   - - CTT TTA ATT GAT AAT TAC CCT GTT CCT CTT TT - #C CCT GAG AGT GGT GAT          1248                                                                        Leu Leu Ile Asp Asn Tyr Pro Val Pro Leu Ph - #e Pro Glu Ser Gly Asp                    400          - #       405          - #       410                       - - TTC ATA AGT AGT AAG CAC CAT ACT GTA GGA AA - #G AAA ACC TAT CAA GTA          1296                                                                        Phe Ile Ser Ser Lys His His Thr Val Gly Ly - #s Lys Thr Tyr Gln Val                415              - #   420              - #   425                           - - GAA GCA TGT TGC AGT AAT CTA AGC TAT GTA AA - #A TTT GGT ATG TAT TAT          1344                                                                        Glu Ala Cys Cys Ser Asn Leu Ser Tyr Val Ly - #s Phe Gly Met Tyr Tyr            430                 4 - #35                 4 - #40                 4 -       #45                                                                               - - GAA GCC CCA CCT AAA GAA GAA GAA AAA GAA AA - #A GAA AAA GAC AAA         GAC     1392                                                                     Glu Ala Pro Pro Lys Glu Glu Glu Lys Glu Ly - #s Glu Lys Asp Lys Asp                           450  - #               455  - #               460               - - AAA GAA AAA GAA AAA CAA GCG ACA ACA TCT AT - #C AAG ACT TAT TAT CAA          1440                                                                        Lys Glu Lys Glu Lys Gln Ala Thr Thr Ser Il - #e Lys Thr Tyr Tyr Gln                        465      - #           470      - #           475                   - - TTC TTA TTA GGT CTC CGT ACT CCC AGT TCT GA - #A ATA CCT AAA GAA GGA          1488                                                                        Phe Leu Leu Gly Leu Arg Thr Pro Ser Ser Gl - #u Ile Pro Lys Glu Gly                    480          - #       485          - #       490                       - - AGT GCA AAA TAT CAT GGT AAT TGG TTT GGT TA - #T ATT AGT GAT GGC GAG          1536                                                                        Ser Ala Lys Tyr His Gly Asn Trp Phe Gly Ty - #r Ile Ser Asp Gly Glu                495              - #   500              - #   505                           - - ACA TCT TAC TCC GCC AGT GGT GAT AAG GAA CG - #C AGT AAA AAT GCT GTC          1584                                                                        Thr Ser Tyr Ser Ala Ser Gly Asp Lys Glu Ar - #g Ser Lys Asn Ala Val            510                 5 - #15                 5 - #20                 5 -       #25                                                                               - - GCC GAG TTT AAT GTA AAT TTT GCC GAG AAA AC - #A TTA ACA GGC GAA         TTA     1632                                                                     Ala Glu Phe Asn Val Asn Phe Ala Glu Lys Th - #r Leu Thr Gly Glu Leu                           530  - #               535  - #               540               - - AAA CGA CAC GAT ACT CAA AAT CCC GTA TTT AA - #A ATT AAT GCA ACC TTT          1680                                                                        Lys Arg His Asp Thr Gln Asn Pro Val Phe Ly - #s Ile Asn Ala Thr Phe                        545      - #           550      - #           555                   - - CAA AGT GGT AAG AAT GAC TTC ACT GGT ACA GC - #A ACC GCA AAA GAT TTA          1728                                                                        Gln Ser Gly Lys Asn Asp Phe Thr Gly Thr Al - #a Thr Ala Lys Asp Leu                    560          - #       565          - #       570                       - - GCA ATA GAT GGT AAA AAT ACA CAA GGC ACA TC - #T AAA GTC AAT TTC ACG          1776                                                                        Ala Ile Asp Gly Lys Asn Thr Gln Gly Thr Se - #r Lys Val Asn Phe Thr                575              - #   580              - #   585                           - - GCA ACA GTA AAC GGG GCA TTT TAT GGT CCG CA - #C GCT ACA GAA TTA GGC          1824                                                                        Ala Thr Val Asn Gly Ala Phe Tyr Gly Pro Hi - #s Ala Thr Glu Leu Gly            590                 5 - #95                 6 - #00                 6 -       #05                                                                               - - GGT TAT TTC ACC TAT AAC GGA AAC AAT CCT AC - #A GAT AAA AAT TCA         TCA     1872                                                                     Gly Tyr Phe Thr Tyr Asn Gly Asn Asn Pro Th - #r Asp Lys Asn Ser Ser                           610  - #               615  - #               620               - - TCC AAT TCA GAA AAG GCA AGA GCT GCC GTT GT - #G TTT GGA GCT AAA AAA          1920                                                                        Ser Asn Ser Glu Lys Ala Arg Ala Ala Val Va - #l Phe Gly Ala Lys Lys                        625      - #           630      - #           635                   - - CAA CAA GTA GAA ACA ACC  AA  GTAATGGAAT AC - #TAAA A ATG ACT AAA         AAA    1969                                                                      Gln Gln Val Glu Thr Thr  Lys      - #               Met Thr - #Lys Lys                640          - #                  - #          645                      - - CCC TAT TTT CGC CTA AGT ATT ATT TCT TGT CT - #T TTA ATT TCA TGC TAT          2017                                                                        Pro Tyr Phe Arg Leu Ser Ile Ile Ser Cys Le - #u Leu Ile Ser Cys Tyr                650              - #   655              - #   660                           - - GTA AAA GCA GAA ACT CAA AGT ATA AAA GAT AC - #A AAA GAA GCT ATA TCA          2065                                                                        Val Lys Ala Glu Thr Gln Ser Ile Lys Asp Th - #r Lys Glu Ala Ile Ser            665                 6 - #70                 6 - #75                 6 -       #80                                                                               - - TCT GAA GTG GAC ACT CAA AGT ACA GAA GAT TC - #A GAA TTA GAA ACT         ATC     2113                                                                     Ser Glu Val Asp Thr Gln Ser Thr Glu Asp Se - #r Glu Leu Glu Thr Ile                           685  - #               690  - #               695               - - TCA GTC ACT GCA GAA AAA GTT AGA GAT CGT AA - #A GAT AAT GAA GTA ACT          2161                                                                        Ser Val Thr Ala Glu Lys Val Arg Asp Arg Ly - #s Asp Asn Glu Val Thr                        700      - #           705      - #           710                   - - GGA CTT GGC AAA ATT ATA AAA ACT AGT GAA AG - #T ATC AGC CGA GAA CAA          2209                                                                        Gly Leu Gly Lys Ile Ile Lys Thr Ser Glu Se - #r Ile Ser Arg Glu Gln                    715          - #       720          - #       725                       - - GTA TTA AAT ATT CGT GAT CTA ACA CGC TAT GA - #T CCA GGG ATT TCA GTT          2257                                                                        Val Leu Asn Ile Arg Asp Leu Thr Arg Tyr As - #p Pro Gly Ile Ser Val                730              - #   735              - #   740                           - - GTA GAA CAA GGT CGC GGT GCA AGT TCT GGA TA - #T TCT ATT CGT GGT ATG          2305                                                                        Val Glu Gln Gly Arg Gly Ala Ser Ser Gly Ty - #r Ser Ile Arg Gly Met            745                 7 - #50                 7 - #55                 7 -       #60                                                                               - - GAC AGA AAT AGA GTT GCT TTA TTA GTA GAT GG - #T TTA CCT CAA ACG         CAA     2353                                                                     Asp Arg Asn Arg Val Ala Leu Leu Val Asp Gl - #y Leu Pro Gln Thr Gln                           765  - #               770  - #               775               - - TCT TAT GTA GTG CAA AGC CCT TTA GTT GCT CG - #T TCA GGA TAT TCT GGC          2401                                                                        Ser Tyr Val Val Gln Ser Pro Leu Val Ala Ar - #g Ser Gly Tyr Ser Gly                        780      - #           785      - #           790                   - - ACT GGT GCA ATT AAT GAA ATT GAA TAT GAA AA - #T GTA AAG GCC GTC GAA          2449                                                                        Thr Gly Ala Ile Asn Glu Ile Glu Tyr Glu As - #n Val Lys Ala Val Glu                    795          - #       800          - #       805                       - - ATA AGC AAG GGG GGG AGT TCT TCT GAG TAT GG - #T AAT GGA GCA CTA GCT          2497                                                                        Ile Ser Lys Gly Gly Ser Ser Ser Glu Tyr Gl - #y Asn Gly Ala Leu Ala                810              - #   815              - #   820                           - - GGT TCT GTA ACA TTT CAA AGC AAA TCA GCA GC - #C GAT ATC TTA GAA GGA          2545                                                                        Gly Ser Val Thr Phe Gln Ser Lys Ser Ala Al - #a Asp Ile Leu Glu Gly            825                 8 - #30                 8 - #35                 8 -       #40                                                                               - - GAC AAA TCA TGG GGA ATT CAA ACT AAA AAT GC - #T TAT TCA AGC AAA         AAT     2593                                                                     Asp Lys Ser Trp Gly Ile Gln Thr Lys Asn Al - #a Tyr Ser Ser Lys Asn                           845  - #               850  - #               855               - - AAA GGC TTT ACC CAT TCT TTA GCT GTA GCA GG - #A AAA CAA GGT GGA TTT          2641                                                                        Lys Gly Phe Thr His Ser Leu Ala Val Ala Gl - #y Lys Gln Gly Gly Phe                        860      - #           865      - #           870                   - - GAA GGG GTC GCC ATT TAC ACT CAC CGA AAT TC - #A ATT GAA ACC CAA GTC          2689                                                                        Glu Gly Val Ala Ile Tyr Thr His Arg Asn Se - #r Ile Glu Thr Gln Val                    875          - #       880          - #       885                       - - CAT AAA GAT GCA TTA AAA GGC GTG CAA AGT TA - #T GAT CGA TTC ATC GCC          2737                                                                        His Lys Asp Ala Leu Lys Gly Val Gln Ser Ty - #r Asp Arg Phe Ile Ala                890              - #   895              - #   900                           - - ACA ACA GAG GAT CAA TCT GCA TAC TTT GTG AT - #G CAA GAT GAG TGT CTA          2785                                                                        Thr Thr Glu Asp Gln Ser Ala Tyr Phe Val Me - #t Gln Asp Glu Cys Leu            905                 9 - #10                 9 - #15                 9 -       #20                                                                               - - GAT GGT TAT GAC AAG TGT AAA ACT TCA CCC AA - #A CGA CCT GCG ACT         TTA     2833                                                                     Asp Gly Tyr Asp Lys Cys Lys Thr Ser Pro Ly - #s Arg Pro Ala Thr Leu                           925  - #               930  - #               935               - - TCC ACC CAA AGA GAA ACC GTA AGC GTT TCA GA - #T TAT ACG GGG GCT AAC          2881                                                                        Ser Thr Gln Arg Glu Thr Val Ser Val Ser As - #p Tyr Thr Gly Ala Asn                        940      - #           945      - #           950                   - - CGT ATC AAA CCT AAT CCA ATG AAA TAT GAA AG - #C CAG TCT TGG TTT TTA          2929                                                                        Arg Ile Lys Pro Asn Pro Met Lys Tyr Glu Se - #r Gln Ser Trp Phe Leu                    955          - #       960          - #       965                       - - AGA GGA GGT TAT CAT TTT TCT GAA CAA CAC TA - #T ATT GGT GGT ATT TTT          2977                                                                        Arg Gly Gly Tyr His Phe Ser Glu Gln His Ty - #r Ile Gly Gly Ile Phe                970              - #   975              - #   980                           - - GAA TTC ACA CAA CAA AAA TTT GAT ATC CGT GA - #T ATG ACA TTT CCC GCT          3025                                                                        Glu Phe Thr Gln Gln Lys Phe Asp Ile Arg As - #p Met Thr Phe Pro Ala            985                 9 - #90                 9 - #95                 1 -       #000                                                                              - - TAT TTA AGG CCA ACA GAA GAC AAG GAT TTA CA - #A AGT CGC CCT TTT         TAT     3073                                                                     Tyr Leu Arg Pro Thr Glu Asp Lys Asp Leu Gl - #n Ser Arg Pro Phe Tyr                           1005 - #               1010  - #              1015              - - CCA AAG CAA GAT TAT GGT GCA TAT CAA CAT AT - #T GGT GAT GGC AGA GGC          3121                                                                        Pro Lys Gln Asp Tyr Gly Ala Tyr Gln His Il - #e Gly Asp Gly Arg Gly                        1020     - #           1025      - #          1030                  - - GTT AAA TAT GCA AGT GGG CTT TAT TTC GAT GA - #A CAC CAT AGA AAA CAG          3169                                                                        Val Lys Tyr Ala Ser Gly Leu Tyr Phe Asp Gl - #u His His Arg Lys Gln                    1035         - #       1040          - #      1045                      - - CGT GTA GGT ATT GAA TAT ATT TAC GAA AAT AA - #G AAC AAA GCG GGC ATC          3217                                                                        Arg Val Gly Ile Glu Tyr Ile Tyr Glu Asn Ly - #s Asn Lys Ala Gly Ile                1050             - #   1055              - #  1060                          - - ATT GAC AAA GCG GTG TTA AGT GCT AAT CAA CA - #A ACA TCA TAC TTG ACA          3265                                                                        Ile Asp Lys Ala Val Leu Ser Ala Asn Gln Gl - #n Thr Ser Tyr Leu Thr            1065                1070 - #                1075 - #               1080         - - GTT ATA TGC GAC ATA CGC ATT GCA GTC TTT AT - #C CAT AAT CCA AGT AAG          3313                                                                        Val Ile Cys Asp Ile Arg Ile Ala Val Phe Il - #e His Asn Pro Ser Lys                            1085 - #               1090  - #              1095              - - AAT TGC CGC CCA ACA CTT GAT AAA CCT TAT TC - #A TAC TAT CAT TCT GAT          3361                                                                        Asn Cys Arg Pro Thr Leu Asp Lys Pro Tyr Se - #r Tyr Tyr His Ser Asp                        1100     - #           1105      - #          1110                  - - AGA AAT GTT TAT AAA GAA AAA CAT AAC ATG TT - #G CAA TTG AAT TTA GAG          3409                                                                        Arg Asn Val Tyr Lys Glu Lys His Asn Met Le - #u Gln Leu Asn Leu Glu                    1115         - #       1120          - #      1125                      - - AAA AAA ATT CAA CAA AAT TGG CTT ACT CAT CA - #A ATT GCC TTC AAT CTT          3457                                                                        Lys Lys Ile Gln Gln Asn Trp Leu Thr His Gl - #n Ile Ala Phe Asn Leu                1130             - #   1135              - #  1140                          - - GGT TTT GAT GAC TTT ACT TCC GCA CTT CAG CA - #T AAA GAT TAT TTA ACT          3505                                                                        Gly Phe Asp Asp Phe Thr Ser Ala Leu Gln Hi - #s Lys Asp Tyr Leu Thr            1145                1150 - #                1155 - #               1160         - - CGA CGT GTT ATC GCT ACG GCA AGT AGT ATT TC - #A GAG AAA CGT GGT GAA          3553                                                                        Arg Arg Val Ile Ala Thr Ala Ser Ser Ile Se - #r Glu Lys Arg Gly Glu                            1165 - #               1170  - #              1175              - - GCA AGA AGA AAT GGT TTA CAA TCA AGT CCT TA - #C TTA TAC CCA ACA CCA          3601                                                                        Ala Arg Arg Asn Gly Leu Gln Ser Ser Pro Ty - #r Leu Tyr Pro Thr Pro                        1180     - #           1185      - #          1190                  - - AAA GCA GAG TTG GTA GGA GGA GAT CTT TGT AA - #T TAT CAA GGT AAG TCC          3649                                                                        Lys Ala Glu Leu Val Gly Gly Asp Leu Cys As - #n Tyr Gln Gly Lys Ser                    1195         - #       1200          - #      1205                      - - TCT AAT TAC AGT GAC TGT AAA GTG CGG TTA AT - #T AAA GGG AAA AAT TAT          3697                                                                        Ser Asn Tyr Ser Asp Cys Lys Val Arg Leu Il - #e Lys Gly Lys Asn Tyr                1210             - #   1215              - #  1220                          - - TAT TTC GCA GCA CGC AAT AAT ATG GCA TTA GG - #G AAA TAC GTT GAT TTA          3745                                                                        Tyr Phe Ala Ala Arg Asn Asn Met Ala Leu Gl - #y Lys Tyr Val Asp Leu            1225                1230 - #                1235 - #               1240         - - GGT TTA GGT ATG AGG TAT GAC GTA TCT CGT AC - #A AAA GCT AAT GAA TCA          3793                                                                        Gly Leu Gly Met Arg Tyr Asp Val Ser Arg Th - #r Lys Ala Asn Glu Ser                            1245 - #               1250  - #              1255              - - ACT ATT AGT GTT GGT AAA TTT AAA AAT TTC TC - #T TGG AAT ACT GGT ATT          3841                                                                        Thr Ile Ser Val Gly Lys Phe Lys Asn Phe Se - #r Trp Asn Thr Gly Ile                        1260     - #           1265      - #          1270                  - - GTC ATA AAA CCA ACG GAA TGG CTT GAT CTT TC - #T TAT CGC CTT TCT ACT          3889                                                                        Val Ile Lys Pro Thr Glu Trp Leu Asp Leu Se - #r Tyr Arg Leu Ser Thr                    1275         - #       1280          - #      1285                      - - GGA TTT AGA AAT CCT AGT TTT GCT GAA ATG TA - #T GGT TGG CGG TAT GGT          3937                                                                        Gly Phe Arg Asn Pro Ser Phe Ala Glu Met Ty - #r Gly Trp Arg Tyr Gly                1290             - #   1295              - #  1300                          - - GGC AAG GAT ACC GAT GTT TAT ATA GGT AAA TT - #T AAG CCT GAA ACA TCT          3985                                                                        Gly Lys Asp Thr Asp Val Tyr Ile Gly Lys Ph - #e Lys Pro Glu Thr Ser            1305                1310 - #                1315 - #               1320         - - CGT AAC CAA GAG TTT GGT CTC GCT CTA AAA GG - #G GAT TTT GGT AAT ATT          4033                                                                        Arg Asn Gln Glu Phe Gly Leu Ala Leu Lys Gl - #y Asp Phe Gly Asn Ile                            1325 - #               1330  - #              1335              - - GAG ATC AGT CAT TTT AGT AAT GCT TAT CGA AA - #T CTT ATC GCC TTT GCT          4081                                                                        Glu Ile Ser His Phe Ser Asn Ala Tyr Arg As - #n Leu Ile Ala Phe Ala                        1340     - #           1345      - #          1350                  - - GAA GAA CTT AGT AAA AAT GGA ACT ACT GGA AA - #G GGC AAT TAT GGA TAT          4129                                                                        Glu Glu Leu Ser Lys Asn Gly Thr Thr Gly Ly - #s Gly Asn Tyr Gly Tyr                    1355         - #       1360          - #      1365                      - - CAT AAT GCA CAA AAT GCA AAA TTA GTT GGC GT - #A AAT ATA ACT GCG CAA          4177                                                                        His Asn Ala Gln Asn Ala Lys Leu Val Gly Va - #l Asn Ile Thr Ala Gln                1370             - #   1375              - #  1380                          - - TTA GAT TTT AAT GGT TTA TGG AAA CGT ATT CC - #C TAC GGT TGG TAT GCA          4225                                                                        Leu Asp Phe Asn Gly Leu Trp Lys Arg Ile Pr - #o Tyr Gly Trp Tyr Ala            1385                1390 - #                1395 - #               1400         - - ACA TTT GCT TAT AAC CGA GTA AAA GTT AAA GA - #T CAA AAA ATC AAT GCT          4273                                                                        Thr Phe Ala Tyr Asn Arg Val Lys Val Lys As - #p Gln Lys Ile Asn Ala                            1405 - #               1410  - #              1415              - - GGT TTA GCT TCC GTA AGC AGT TAT TTA TTT GA - #T GCC ATT CAG CCC AGC          4321                                                                        Gly Leu Ala Ser Val Ser Ser Tyr Leu Phe As - #p Ala Ile Gln Pro Ser                        1420     - #           1425      - #          1430                  - - CGT TAT ATC ATT GGT TTA GGC TAT GAT CAT CC - #A AGT AAT ACT TGG GGA          4369                                                                        Arg Tyr Ile Ile Gly Leu Gly Tyr Asp His Pr - #o Ser Asn Thr Trp Gly                    1435         - #       1440          - #      1445                      - - ATT AAG ACA ATG TTT ACT CAA TCA AAA GCA AA - #A TCT CAA AAT GAA TTG          4417                                                                        Ile Lys Thr Met Phe Thr Gln Ser Lys Ala Ly - #s Ser Gln Asn Glu Leu                1450             - #   1455              - #  1460                          - - CTA GGA AAA CGT GCA TTG GGT AAC AAT TCA AG - #G AAT GTA AAA TCA ACA          4465                                                                        Leu Gly Lys Arg Ala Leu Gly Asn Asn Ser Ar - #g Asn Val Lys Ser Thr            1465                1470 - #                1475 - #               1480         - - AGA AAA CTT ACT CGG GCA TGG CAT ATC TTA GA - #T GTA TCG GGT TAT TAC          4513                                                                        Arg Lys Leu Thr Arg Ala Trp His Ile Leu As - #p Val Ser Gly Tyr Tyr                            1485 - #               1490  - #              1495              - - ATG GTG AAT AGA AGT ATT TTG TTC CGA TTA GG - #A GTA TAT AAT TTA TTA          4561                                                                        Met Val Asn Arg Ser Ile Leu Phe Arg Leu Gl - #y Val Tyr Asn Leu Leu                        1500     - #           1505      - #          1510                  - - AAC TAT CGC TAT GTC ACT TGG GAA GCG GTG CG - #T CAA ACA GCA CAA GGT          4609                                                                        Asn Tyr Arg Tyr Val Thr Trp Glu Ala Val Ar - #g Gln Thr Ala Gln Gly                    1515         - #       1520          - #      1525                      - - GCG GTC AAT CAA CAT CAA AAT GTT GGT AAC TA - #T ACT CGC TAC GCA GCA          4657                                                                        Ala Val Asn Gln His Gln Asn Val Gly Asn Ty - #r Thr Arg Tyr Ala Ala                1530             - #   1535              - #  1540                          - - TCA GGA CGA AAC TAT ACC TTA ACA TTA GAA AT - #G AAA TTC TAA                  - #4699                                                                     Ser Gly Arg Asn Tyr Thr Leu Thr Leu Glu Me - #t Lys Phe                        1545                1550 - #                1555                                - -  - - (2) INFORMATION FOR SEQ ID NO:2:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 5033 base - #pairs                                                 (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: double                                                       (D) TOPOLOGY: linear                                                  - -     (ix) FEATURE:                                                                   (A) NAME/KEY: CDS                                                              (B) LOCATION: join(169..21 - #48, 2165..4900)                         - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:2:                         - - GCCCAAGCTA CATTGGTTAA TGATAAGCCT ATAAATGATA AGAAAGAAAT TT -              #GTTTTACG     60                                                                  - - CCATTTTTCA TATTTTATCC ATGAACTTAA AAAACTCTAA CTTGACATTA TT -             #ACAAAAAA    120                                                                  - - AGATCAATAA TGCGAATTAT TATCAATTTT GTATGAGTAT ATAATTCT ATG - #AAA         TCT     177                                                                                        - #                  - #                 Met - # Lys       Ser                                                                                                - #                  - #                  - # 1              - - GTA CCT CTT ATC TCT GGT GGA CTT TCC TTT TT - #A CTA AGT GCT TGT AGC           225                                                                        Val Pro Leu Ile Ser Gly Gly Leu Ser Phe Le - #u Leu Ser Ala Cys Ser                  5            - #      10            - #      15                           - - GGA GGG GGG TCT TTT GAT GTA GAT AAC GTC TC - #T AAT ACC CCC TCT TCT           273                                                                        Gly Gly Gly Ser Phe Asp Val Asp Asn Val Se - #r Asn Thr Pro Ser Ser             20                 - # 25                 - # 30                 - # 35        - - AAA CCA CGT TAT CAA GAC GAT ACC TCG AAT CA - #A AGA AAA AAA TCT AAT           321                                                                        Lys Pro Arg Tyr Gln Asp Asp Thr Ser Asn Gl - #n Arg Lys Lys Ser Asn                             40 - #                 45 - #                 50               - - TTG AAA AAG TTG TTC ATT CCT TCT TTA GGA GG - #A GGG ATG AAA TTG GTG           369                                                                        Leu Lys Lys Leu Phe Ile Pro Ser Leu Gly Gl - #y Gly Met Lys Leu Val                         55     - #             60     - #             65                   - - GCT CAG AAT CTT CGT GGT AAT AAA GAA CCT AG - #T TTC TTA AAT GAA GAT           417                                                                        Ala Gln Asn Leu Arg Gly Asn Lys Glu Pro Se - #r Phe Leu Asn Glu Asp                     70         - #         75         - #         80                       - - GAC TAT ATA TCA TAT TTT TCC TCA CTT TCT AC - #G ATT GAA AAG GAT GTT           465                                                                        Asp Tyr Ile Ser Tyr Phe Ser Ser Leu Ser Th - #r Ile Glu Lys Asp Val                 85             - #     90             - #     95                           - - AAA GAT AAC AAT AAA AAC GGG GCG GAC CTT AT - #T GGC TCA ATA GAC GAG           513                                                                        Lys Asp Asn Asn Lys Asn Gly Ala Asp Leu Il - #e Gly Ser Ile Asp Glu            100                 1 - #05                 1 - #10                 1 -       #15                                                                               - - CCT AGT ACA ACA AAT CCA CCC GAA AAG CAT CA - #T GGA CAA AAA TAT         GTA      561                                                                     Pro Ser Thr Thr Asn Pro Pro Glu Lys His Hi - #s Gly Gln Lys Tyr Val                           120  - #               125  - #               130               - - TAT TCA GGG CTT TAT TAT ACT CCA TCG TGG AG - #T TTA AAC GAT TCT AAA           609                                                                        Tyr Ser Gly Leu Tyr Tyr Thr Pro Ser Trp Se - #r Leu Asn Asp Ser Lys                        135      - #           140      - #           145                   - - AAC AAG TTT TAT TTA GGT TAC TAT GGA TAT GC - #G TTT TAT TAT GGT AAT           657                                                                        Asn Lys Phe Tyr Leu Gly Tyr Tyr Gly Tyr Al - #a Phe Tyr Tyr Gly Asn                    150          - #       155          - #       160                       - - AAA ACT GCA ACA AAC TTG CCA GTA AAC GGT GT - #A GCT AAA TAC AAA GGA           705                                                                        Lys Thr Ala Thr Asn Leu Pro Val Asn Gly Va - #l Ala Lys Tyr Lys Gly                165              - #   170              - #   175                           - - ACT TGG GAT TTC ATC ACT GCA ACT AAA AAT GG - #C AAA CGT TAT CCT TTG           753                                                                        Thr Trp Asp Phe Ile Thr Ala Thr Lys Asn Gl - #y Lys Arg Tyr Pro Leu            180                 1 - #85                 1 - #90                 1 -       #95                                                                               - - TTA AGT AAT GGC AGT CAC GCT TAT TAT CGA CG - #T AGT GCA ATT CCA         GAA      801                                                                     Leu Ser Asn Gly Ser His Ala Tyr Tyr Arg Ar - #g Ser Ala Ile Pro Glu                           200  - #               205  - #               210               - - GAT ATT GAT TTA GAA AAT GAT TCA AAG AAT GG - #T GAT ATA GGC TTA ATA           849                                                                        Asp Ile Asp Leu Glu Asn Asp Ser Lys Asn Gl - #y Asp Ile Gly Leu Ile                        215      - #           220      - #           225                   - - AGT GAA TTT AGT GCA GAT TTT GGG ACT AAA AA - #A CTG ACA GGA CAA CTG           897                                                                        Ser Glu Phe Ser Ala Asp Phe Gly Thr Lys Ly - #s Leu Thr Gly Gln Leu                    230          - #       235          - #       240                       - - TCT TAC ACC AAA AGA AAA ACT AAT AAT CAA CC - #A TAT GAA AAG AAA AAA           945                                                                        Ser Tyr Thr Lys Arg Lys Thr Asn Asn Gln Pr - #o Tyr Glu Lys Lys Lys                245              - #   250              - #   255                           - - CTC TAT GAT ATA GAT GCC GAT ATT TAT AGT AA - #T AGA TTC AGG GGT ACA           993                                                                        Leu Tyr Asp Ile Asp Ala Asp Ile Tyr Ser As - #n Arg Phe Arg Gly Thr            260                 2 - #65                 2 - #70                 2 -       #75                                                                               - - GTA AAG CCA ACC GAA AAA GAT TCT GAA GAA CA - #T CCC TTT ACC AGC         GAG     1041                                                                     Val Lys Pro Thr Glu Lys Asp Ser Glu Glu Hi - #s Pro Phe Thr Ser Glu                           280  - #               285  - #               290               - - GGA ACA TTA GAA GGT GGT TTT TAT GGG CCT AA - #T GCT GAA GAA CTA GGG          1089                                                                        Gly Thr Leu Glu Gly Gly Phe Tyr Gly Pro As - #n Ala Glu Glu Leu Gly                        295      - #           300      - #           305                   - - GGG AAA TTT TTA GCT ACG GAT AAC CGA GTT TT - #T GGG GTA TTT AGT GCC          1137                                                                        Gly Lys Phe Leu Ala Thr Asp Asn Arg Val Ph - #e Gly Val Phe Ser Ala                    310          - #       315          - #       320                       - - AAA GAA ACG GAA GAA ACA AAA AAG GAA GCG TT - #A TCC AAG GAA ACC TTA          1185                                                                        Lys Glu Thr Glu Glu Thr Lys Lys Glu Ala Le - #u Ser Lys Glu Thr Leu                325              - #   330              - #   335                           - - ATT GAT GGC AAG CTA ATT ACT TTC TCT ACT AA - #A AAA ACC GAT GCA AAA          1233                                                                        Ile Asp Gly Lys Leu Ile Thr Phe Ser Thr Ly - #s Lys Thr Asp Ala Lys            340                 3 - #45                 3 - #50                 3 -       #55                                                                               - - ACC AAT GCA ACA ACC AGT ACC GCA GCT AAT AC - #A ACA ACC GAT ACA         ACC     1281                                                                     Thr Asn Ala Thr Thr Ser Thr Ala Ala Asn Th - #r Thr Thr Asp Thr Thr                           360  - #               365  - #               370               - - GCC AAT ACA ATA ACC GAT GAA AAA AAC TTT AA - #G ACG GAA GAT ATA TCA          1329                                                                        Ala Asn Thr Ile Thr Asp Glu Lys Asn Phe Ly - #s Thr Glu Asp Ile Ser                        375      - #           380      - #           385                   - - AGT TTT GGT GAA GCT GAT TAT CTG TTA ATT GA - #C AAA TAT CCT ATT CCA          1377                                                                        Ser Phe Gly Glu Ala Asp Tyr Leu Leu Ile As - #p Lys Tyr Pro Ile Pro                    390          - #       395          - #       400                       - - CTT TTA CCT GAT AAA AAT ACT AAT GAT TTC AT - #A AGT AGT AAG CAT CAT          1425                                                                        Leu Leu Pro Asp Lys Asn Thr Asn Asp Phe Il - #e Ser Ser Lys His His                405              - #   410              - #   415                           - - ACT GTA GGA AAT AAA CGC TAT AAA GTG GAA GC - #A TGT TGC AGT AAT CTA          1473                                                                        Thr Val Gly Asn Lys Arg Tyr Lys Val Glu Al - #a Cys Cys Ser Asn Leu            420                 4 - #25                 4 - #30                 4 -       #35                                                                               - - AGC TAT GTG AAA TTT GGT ATG TAT TAT GAA GA - #C CCA CTT AAA GAA         AAA     1521                                                                     Ser Tyr Val Lys Phe Gly Met Tyr Tyr Glu As - #p Pro Leu Lys Glu Lys                           440  - #               445  - #               450               - - GAA ACA GAA ACA GAA ACA GAA ACA GAA AAA GA - #C AAA GAA AAA GAA AAA          1569                                                                        Glu Thr Glu Thr Glu Thr Glu Thr Glu Lys As - #p Lys Glu Lys Glu Lys                        455      - #           460      - #           465                   - - GAA AAA GAC AAA GAC AAA GAA AAA CAA ACG GC - #G GCA ACG ACC AAC ACT          1617                                                                        Glu Lys Asp Lys Asp Lys Glu Lys Gln Thr Al - #a Ala Thr Thr Asn Thr                    470          - #       475          - #       480                       - - TAT TAT CAA TTC TTA TTA GGT CAC CGT ACT CC - #C AAG GAC GAC ATA CCT          1665                                                                        Tyr Tyr Gln Phe Leu Leu Gly His Arg Thr Pr - #o Lys Asp Asp Ile Pro                485              - #   490              - #   495                           - - AAA ACA GGA AGT GCA AAA TAT CAT GGT AGT TG - #G TTT GGT TAT ATT ACT          1713                                                                        Lys Thr Gly Ser Ala Lys Tyr His Gly Ser Tr - #p Phe Gly Tyr Ile Thr            500                 5 - #05                 5 - #10                 5 -       #15                                                                               - - GAC GGT AAG ACA TCT TAC TCC CCC AGT GGT GA - #T AAG AAA CGC GAT         AAA     1761                                                                     Asp Gly Lys Thr Ser Tyr Ser Pro Ser Gly As - #p Lys Lys Arg Asp Lys                           520  - #               525  - #               530               - - AAT GCT GTC GCC GAG TTT AAT GTT GAT TTT GC - #C GAG AAA AAG CTA ACA          1809                                                                        Asn Ala Val Ala Glu Phe Asn Val Asp Phe Al - #a Glu Lys Lys Leu Thr                        535      - #           540      - #           545                   - - GGC GAA TTA AAA CGA CAC GAT ACT GGA AAT CC - #C GTA TTT AGT ATT GAG          1857                                                                        Gly Glu Leu Lys Arg His Asp Thr Gly Asn Pr - #o Val Phe Ser Ile Glu                    550          - #       555          - #       560                       - - GCA AAC TTT AAT AAT AGT AGT AAT GCC TTC AC - #T GGT ACA GCA ACC GCA          1905                                                                        Ala Asn Phe Asn Asn Ser Ser Asn Ala Phe Th - #r Gly Thr Ala Thr Ala                565              - #   570              - #   575                           - - ACA AAT TTT GTA ATA GAT GGT AAA AAT AGT CA - #A AAT AAA AAT ACC CCA          1953                                                                        Thr Asn Phe Val Ile Asp Gly Lys Asn Ser Gl - #n Asn Lys Asn Thr Pro            580                 5 - #85                 5 - #90                 5 -       #95                                                                               - - ATT AAT ATT ACA ACT AAA GTA AAC GGG GCA TT - #T TAT GGA CCT AAG         GCT     2001                                                                     Ile Asn Ile Thr Thr Lys Val Asn Gly Ala Ph - #e Tyr Gly Pro Lys Ala                           600  - #               605  - #               610               - - TCT GAA TTA GGC GGT TAT TTC ACT TAT AAC GG - #A AAT TCT ACA GCT ACA          2049                                                                        Ser Glu Leu Gly Gly Tyr Phe Thr Tyr Asn Gl - #y Asn Ser Thr Ala Thr                        615      - #           620      - #           625                   - - AAT TCT GAA AGT TCC TCA ACC GTA TCT TCA TC - #A TCC AAT TCA AAA AAT          2097                                                                        Asn Ser Glu Ser Ser Ser Thr Val Ser Ser Se - #r Ser Asn Ser Lys Asn                    630          - #       635          - #       640                       - - GCA AGA GCT GCA GTT GTC TTT GGT GCG AGA CA - #A CAA GTA GAA ACA ACC          2145                                                                        Ala Arg Ala Ala Val Val Phe Gly Ala Arg Gl - #n Gln Val Glu Thr Thr                645              - #   650              - #   655                           - - AAA TAATGGAATA CTAAAA ATG ACT AAA AAA CCC TAT - #TTT CGC CTA AGT            2194                                                                         Lys                  - # Met Thr Lys Lys Pro Tyr Phe Arg Leu Ser               660                  - #                 665 - #                 670            - - ATT ATT TCT TGT CTT TTA ATT TCA TGC TAT GT - #A AAA GCA GAA ACT CAA          2242                                                                        Ile Ile Ser Cys Leu Leu Ile Ser Cys Tyr Va - #l Lys Ala Glu Thr Gln                            675  - #               680  - #               685               - - AGT ATA AAA GAT ACA AAA GAA GCT ATA TCA TC - #T GAA GTG GAC ACT CAA          2290                                                                        Ser Ile Lys Asp Thr Lys Glu Ala Ile Ser Se - #r Glu Val Asp Thr Gln                        690      - #           695      - #           700                   - - AGT ACA GAA GAT TCA GAA TTA GAA ACT ATC TC - #A GTC ACT GCA GAA AAA          2338                                                                        Ser Thr Glu Asp Ser Glu Leu Glu Thr Ile Se - #r Val Thr Ala Glu Lys                    705          - #       710          - #       715                       - - ATA AGA GAT CGT AAA GAT AAT GAA GTA ACT GG - #A CTT GGC AAA ATT ATC          2386                                                                        Ile Arg Asp Arg Lys Asp Asn Glu Val Thr Gl - #y Leu Gly Lys Ile Ile                720              - #   725              - #   730                           - - AAA ACT AGT GAA AGT ATC AGC CGA GAA CAA GT - #A TTA AAT ATT CGT GAT          2434                                                                        Lys Thr Ser Glu Ser Ile Ser Arg Glu Gln Va - #l Leu Asn Ile Arg Asp            735                 7 - #40                 7 - #45                 7 -       #50                                                                               - - CTA ACA CGC TAT GAT CCA GGG ATT TCA GTT GT - #A GAA CAA GGT CGC         GGT     2482                                                                     Leu Thr Arg Tyr Asp Pro Gly Ile Ser Val Va - #l Glu Gln Gly Arg Gly                           755  - #               760  - #               765               - - GCA AGT TCT GGA TAT TCT ATT CGT GGT ATG GA - #C AGA AAT AGA GTT GCT          2530                                                                        Ala Ser Ser Gly Tyr Ser Ile Arg Gly Met As - #p Arg Asn Arg Val Ala                        770      - #           775      - #           780                   - - TTA TTA GTA GAT GGT TTA CCT CAA ACG CAA TC - #T TAT GTA GTG CAA AGC          2578                                                                        Leu Leu Val Asp Gly Leu Pro Gln Thr Gln Se - #r Tyr Val Val Gln Ser                    785          - #       790          - #       795                       - - CCT TTA GTT GCT CGT TCA GGA TAT TCT GGC AC - #T GGT GCA ATT AAT GAA          2626                                                                        Pro Leu Val Ala Arg Ser Gly Tyr Ser Gly Th - #r Gly Ala Ile Asn Glu                800              - #   805              - #   810                           - - ATT GAA TAT GAA AAT GTA AAG GCC GTC GAA AT - #A AGC AAG GGG GGG AGT          2674                                                                        Ile Glu Tyr Glu Asn Val Lys Ala Val Glu Il - #e Ser Lys Gly Gly Ser            815                 8 - #20                 8 - #25                 8 -       #30                                                                               - - TCT TCT GAG TAT GGT AAT GGA GCA CTA GCT GG - #T TCT GTA ACA TTT         CAA     2722                                                                     Ser Ser Glu Tyr Gly Asn Gly Ala Leu Ala Gl - #y Ser Val Thr Phe Gln                           835  - #               840  - #               845               - - AGC AAA TCA GCA GCC GAT ATC TTA GAA GGA GA - #C AAA TCA TGG GGA ATT          2770                                                                        Ser Lys Ser Ala Ala Asp Ile Leu Glu Gly As - #p Lys Ser Trp Gly Ile                        850      - #           855      - #           860                   - - CAA ACT AAA AAT GCT TAT TCA AGC AAA AAT AA - #A GGC TTT ACC CAT TCT          2818                                                                        Gln Thr Lys Asn Ala Tyr Ser Ser Lys Asn Ly - #s Gly Phe Thr His Ser                    865          - #       870          - #       875                       - - TTA GCT GTA GCA GGA AAA CAA GGT GGA TTT GA - #A GGG CTA GCC ATT TAC          2866                                                                        Leu Ala Val Ala Gly Lys Gln Gly Gly Phe Gl - #u Gly Leu Ala Ile Tyr                880              - #   885              - #   890                           - - ACT CAA CGA AAT TCA ATT GAA ACC CAA GTC CA - #T AAA GAT GCA TTA AAA          2914                                                                        Thr Gln Arg Asn Ser Ile Glu Thr Gln Val Hi - #s Lys Asp Ala Leu Lys            895                 9 - #00                 9 - #05                 9 -       #10                                                                               - - GGC GTA CAA AGT TAT GAT CGA TTA ATC GCC AC - #A ACA GAT AAA TCT         TCA     2962                                                                     Gly Val Gln Ser Tyr Asp Arg Leu Ile Ala Th - #r Thr Asp Lys Ser Ser                           915  - #               920  - #               925               - - GGA TAC TTT GTG ATA CAA GGT GAG TGT CCA AA - #T GGT GAT GAC AAG TGT          3010                                                                        Gly Tyr Phe Val Ile Gln Gly Glu Cys Pro As - #n Gly Asp Asp Lys Cys                        930      - #           935      - #           940                   - - GCA GCC AAG CCA CCT GCG ACT TTA TCC ACC CA - #A AGC GAA ACC GTA AGC          3058                                                                        Ala Ala Lys Pro Pro Ala Thr Leu Ser Thr Gl - #n Ser Glu Thr Val Ser                    945          - #       950          - #       955                       - - GTT TCA GAT TAT ACG GGG GCT AAC CGT ATC AA - #A CCT AAT CCA ATG AAA          3106                                                                        Val Ser Asp Tyr Thr Gly Ala Asn Arg Ile Ly - #s Pro Asn Pro Met Lys                960              - #   965              - #   970                           - - TAT GAA AGC CAG TCT TGG TTT TTA AGA GGA GG - #G TAT CAT TTT TCT GAA          3154                                                                        Tyr Glu Ser Gln Ser Trp Phe Leu Arg Gly Gl - #y Tyr His Phe Ser Glu            975                 9 - #80                 9 - #85                 9 -       #90                                                                               - - CAA CAT TAT ATT GGT GGT ATT TTT GAA TTC AC - #A CAA CAA AAA TTT         GAT     3202                                                                     Gln His Tyr Ile Gly Gly Ile Phe Glu Phe Th - #r Gln Gln Lys Phe Asp                           995  - #               1000  - #              1005              - - ATC CGT GAT ATG ACA TTT CCC GCT TAT TTA AG - #C CCA ACA GAA AGA CGG          3250                                                                        Ile Arg Asp Met Thr Phe Pro Ala Tyr Leu Se - #r Pro Thr Glu Arg Arg                        1010     - #           1015      - #          1020                  - - GAT GAT AGT AGT CGT TCT TTT TAT CCA ATG CA - #A GAT CAT GGT GCA TAT          3298                                                                        Asp Asp Ser Ser Arg Ser Phe Tyr Pro Met Gl - #n Asp His Gly Ala Tyr                    1025         - #       1030          - #      1035                      - - CAA CAT ATT GAG GAT GGC AGA GGC GTT AAA TA - #T GCA AGT GGG CTT TAT          3346                                                                        Gln His Ile Glu Asp Gly Arg Gly Val Lys Ty - #r Ala Ser Gly Leu Tyr                1040             - #   1045              - #  1050                          - - TTC GAT GAA CAC CAT AGA AAA CAG CGT GTA GG - #T ATT GAA TAT ATT TAC          3394                                                                        Phe Asp Glu His His Arg Lys Gln Arg Val Gl - #y Ile Glu Tyr Ile Tyr            1055                1060 - #                1065 - #               1070         - - GAA AAT AAG AAC AAA GCG GGC ATC ATT GAC AA - #A GCA GTG TTA AGT GCT          3442                                                                        Glu Asn Lys Asn Lys Ala Gly Ile Ile Asp Ly - #s Ala Val Leu Ser Ala                            1075 - #               1080  - #              1085              - - AAT CAA CAA AAC ATC ATA CTT GAC AGT TAT AT - #G CGA CAT ACG CAT TGC          3490                                                                        Asn Gln Gln Asn Ile Ile Leu Asp Ser Tyr Me - #t Arg His Thr His Cys                        1090     - #           1095      - #          1100                  - - AGT CTT TAT CCT AAT CCA AGT AAG AAT TGC CG - #C CCA ACA CTT GAT AAA          3538                                                                        Ser Leu Tyr Pro Asn Pro Ser Lys Asn Cys Ar - #g Pro Thr Leu Asp Lys                    1105         - #       1110          - #      1115                      - - CCT TAT TCA TAC TAT CGT TCT GAT AGA AAT GT - #T TAT AAA GAA AAA CAT          3586                                                                        Pro Tyr Ser Tyr Tyr Arg Ser Asp Arg Asn Va - #l Tyr Lys Glu Lys His                1120             - #   1125              - #  1130                          - - AAT ATG TTG CAA TTG AAT TTA GAG AAA AAA AT - #T CAA CAA AAT TGG CTT          3634                                                                        Asn Met Leu Gln Leu Asn Leu Glu Lys Lys Il - #e Gln Gln Asn Trp Leu            1135                1140 - #                1145 - #               1150         - - ACT CAT CAA ATT GTC TTC AAT CTT GGT TTT GA - #T GAC TTT ACT TCA GCG          3682                                                                        Thr His Gln Ile Val Phe Asn Leu Gly Phe As - #p Asp Phe Thr Ser Ala                            1155 - #               1160  - #              1165              - - CTT CAG CAT AAA GAT TAT TTA ACT CGA CGT GT - #T ATC GCT ACG GCA GAT          3730                                                                        Leu Gln His Lys Asp Tyr Leu Thr Arg Arg Va - #l Ile Ala Thr Ala Asp                        1170     - #           1175      - #          1180                  - - AGT ATT CCA AGG AAA CCT GGT GAA ACT GGT AA - #A CCA AGA AAT GGT TTG          3778                                                                        Ser Ile Pro Arg Lys Pro Gly Glu Thr Gly Ly - #s Pro Arg Asn Gly Leu                    1185         - #       1190          - #      1195                      - - CAA TCA CAA CCT TAC TTA TAC CCA AAA CCA GA - #G CCA TAT TTT GCA GGA          3826                                                                        Gln Ser Gln Pro Tyr Leu Tyr Pro Lys Pro Gl - #u Pro Tyr Phe Ala Gly                1200             - #   1205              - #  1210                          - - CAA GAT CAT TGT AAT TAT CAA GGT AGC TCC TC - #T AAT TAC AGA GAC TGT          3874                                                                        Gln Asp His Cys Asn Tyr Gln Gly Ser Ser Se - #r Asn Tyr Arg Asp Cys            1215                1220 - #                1225 - #               1230         - - AAA GTG CGG TTA ATT AAA GGG AAA AAT TAT TA - #T TTC GCA GCA CGC AAT          3922                                                                        Lys Val Arg Leu Ile Lys Gly Lys Asn Tyr Ty - #r Phe Ala Ala Arg Asn                            1235 - #               1240  - #              1245              - - AAT ATG GCA TTA GGG AAA TAC GTT GAT TTA GG - #T TTA GGT ATT CGG TAT          3970                                                                        Asn Met Ala Leu Gly Lys Tyr Val Asp Leu Gl - #y Leu Gly Ile Arg Tyr                        1250     - #           1255      - #          1260                  - - GAC GTA TCT CGT ACA AAA GCT AAT GAA TCA AC - #T ATT AGT GTT GGT AAA          4018                                                                        Asp Val Ser Arg Thr Lys Ala Asn Glu Ser Th - #r Ile Ser Val Gly Lys                    1265         - #       1270          - #      1275                      - - TTT AAA AAT TTC TCT TGG AAT ACT GGT ATT GT - #C ATA AAA CCA ACG GAA          4066                                                                        Phe Lys Asn Phe Ser Trp Asn Thr Gly Ile Va - #l Ile Lys Pro Thr Glu                1280             - #   1285              - #  1290                          - - TGG CTT GAT CTT TCT TAT CGC CTT TCT ACT GG - #A TTT AGA AAT CCT AGT          4114                                                                        Trp Leu Asp Leu Ser Tyr Arg Leu Ser Thr Gl - #y Phe Arg Asn Pro Ser            1295                1300 - #                1305 - #               1310         - - TTT TCT GAA ATG TAT GGT TGG CGG TAT GGT GG - #C AAG AAT GAC GAG GTT          4162                                                                        Phe Ser Glu Met Tyr Gly Trp Arg Tyr Gly Gl - #y Lys Asn Asp Glu Val                            1315 - #               1320  - #              1325              - - TAT GTA GGT AAA TTT AAG CCT GAA ACA TCT CG - #T AAC CAA GAG TTT GGT          4210                                                                        Tyr Val Gly Lys Phe Lys Pro Glu Thr Ser Ar - #g Asn Gln Glu Phe Gly                        1330     - #           1335      - #          1340                  - - CTC GCT CTA AAA GGG GAT TTT GGT AAT ATT GA - #G ATC AGT CAT TTT AGT          4258                                                                        Leu Ala Leu Lys Gly Asp Phe Gly Asn Ile Gl - #u Ile Ser His Phe Ser                    1345         - #       1350          - #      1355                      - - AAT GCT TAT CGA AAT CTT ATC GCC TTT GCT GA - #A GAA CTT AGT AAA AAT          4306                                                                        Asn Ala Tyr Arg Asn Leu Ile Ala Phe Ala Gl - #u Glu Leu Ser Lys Asn                1360             - #   1365              - #  1370                          - - GGA ACT GGA AAG GGC AAT TAT GGA TAT CAT AA - #T GCA CAA AAT GCA AAA          4354                                                                        Gly Thr Gly Lys Gly Asn Tyr Gly Tyr His As - #n Ala Gln Asn Ala Lys            1375                1380 - #                1385 - #               1390         - - TTA GTT GGC GTA AAT ATA ACT GCA CAA TTA GA - #T TTT AAT GGT TTA TGG          4402                                                                        Leu Val Gly Val Asn Ile Thr Ala Gln Leu As - #p Phe Asn Gly Leu Trp                            1395 - #               1400  - #              1405              - - AAA CGT ATT CCC TAC GGT TGG TAT GCA ACA TT - #T GCT TAT AAC CAA GTA          4450                                                                        Lys Arg Ile Pro Tyr Gly Trp Tyr Ala Thr Ph - #e Ala Tyr Asn Gln Val                        1410     - #           1415      - #          1420                  - - AAA GTT AAA GAT CAA AAA ATC AAT GCT GGT TT - #A GCC TCC GTA AGC AGT          4498                                                                        Lys Val Lys Asp Gln Lys Ile Asn Ala Gly Le - #u Ala Ser Val Ser Ser                    1425         - #       1430          - #      1435                      - - TAT TTA TTT GAT GCC ATT CAG CCC AGC CGT TA - #T ATC ATT GGT TTA GGC          4546                                                                        Tyr Leu Phe Asp Ala Ile Gln Pro Ser Arg Ty - #r Ile Ile Gly Leu Gly                1440             - #   1445              - #  1450                          - - TAT GAT CAT CCA AGT AAT ACT TGG GGA ATT AA - #T ACA ATG TTT ACT CAA          4594                                                                        Tyr Asp His Pro Ser Asn Thr Trp Gly Ile As - #n Thr Met Phe Thr Gln            1455                1460 - #                1465 - #               1470         - - TCA AAA GCA AAA TCT CAA AAT GAA TTG CTA GG - #A AAA CGT GCA TTA GGT          4642                                                                        Ser Lys Ala Lys Ser Gln Asn Glu Leu Leu Gl - #y Lys Arg Ala Leu Gly                            1475 - #               1480  - #              1485              - - AAC AAT TCA AGG GAT GTA AAA TCA ACA AGA AA - #A CTT ACT CGG GCA TGG          4690                                                                        Asn Asn Ser Arg Asp Val Lys Ser Thr Arg Ly - #s Leu Thr Arg Ala Trp                        1490     - #           1495      - #          1500                  - - CAT ATC TTA GAT GTA TCG GGT TAT TAC ATG GC - #G AAT AAA AAT ATT ATG          4738                                                                        His Ile Leu Asp Val Ser Gly Tyr Tyr Met Al - #a Asn Lys Asn Ile Met                    1505         - #       1510          - #      1515                      - - CTT CGA TTA GGG ATA TAT AAT TTA TTC AAC TA - #T CGC TAT GTT ACT TGG          4786                                                                        Leu Arg Leu Gly Ile Tyr Asn Leu Phe Asn Ty - #r Arg Tyr Val Thr Trp                1520             - #   1525              - #  1530                          - - GAA GCG GTG CGT CAA ACA GCA CAA GGT GCG GT - #C AAT CAA CAT CAA AAT          4834                                                                        Glu Ala Val Arg Gln Thr Ala Gln Gly Ala Va - #l Asn Gln His Gln Asn            1535                1540 - #                1545 - #               1550         - - GTT GGT AGC TAT ACT CGC TAC GCA GCA TCA GG - #A CGA AAC TAT ACC TTA          4882                                                                        Val Gly Ser Tyr Thr Arg Tyr Ala Ala Ser Gl - #y Arg Asn Tyr Thr Leu                            1555 - #               1560  - #              1565              - - ACA TTA GAA ATG AAA TTC TAAATTAAAA TGCGCCAGAT GG - #ACTAGATA                 4930                                                                        Thr Leu Glu Met Lys Phe                                                                    1570                                                                - - TGCTATATCT ATACCTTACT GGCGCATCTT TTTCTGTTCT ATAATCTGCT TA -              #AGTGAAAA   4990                                                                  - - ACCAAACTTG GATTTTTTAC AAGATCTTTT CACACATTTA TTG    - #                      503 - #3                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:3:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 5009 base - #pairs                                                 (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: double                                                       (D) TOPOLOGY: linear                                                  - -     (ix) FEATURE:                                                                   (A) NAME/KEY: CDS                                                              (B) LOCATION: join(121..21 - #00, 2117..4852)                         - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:3:                         - - ATTTGTTTTA CGCCATTTTT CATATTTTAT CCATGAACTT AAAAAACTCT AA -              #CTTGACAT     60                                                                  - - TATTACAAAA AAAGATCAAT AATGCGAATT ATTATCAATT TTGTATGAGT AT -             #ATAATTCT    120                                                                  - - ATG AAA TCT GTA CCT CTT ATC TCT GGT GGA CT - #T TCC TTT TTA CTA         AGT      168                                                                     Met Lys Ser Val Pro Leu Ile Ser Gly Gly Le - #u Ser Phe Leu Leu Ser             1               5 - #                 10 - #                 15               - - GCT TGT AGC GGA GGG GGG TCT TTT GAT GTA GA - #T AAC GTC TCT AAT ACC           216                                                                        Ala Cys Ser Gly Gly Gly Ser Phe Asp Val As - #p Asn Val Ser Asn Thr                         20     - #             25     - #             30                   - - CCC TCT TCT AAA CCA CGT TAT CAA GAC GAT AC - #C TCG AAT CAA AGA AAA           264                                                                        Pro Ser Ser Lys Pro Arg Tyr Gln Asp Asp Th - #r Ser Asn Gln Arg Lys                     35         - #         40         - #         45                       - - AAA TCT AAT TTG AAA AAG TTG TTC ATT CCT TC - #T TTA GGA GGA GGG ATG           312                                                                        Lys Ser Asn Leu Lys Lys Leu Phe Ile Pro Se - #r Leu Gly Gly Gly Met                 50             - #     55             - #     60                           - - AAA TTG GTG GCT CAG AAT CTT CGT GGT AAT AA - #A GAA CCT AGT TTC TTA           360                                                                        Lys Leu Val Ala Gln Asn Leu Arg Gly Asn Ly - #s Glu Pro Ser Phe Leu             65                 - # 70                 - # 75                 - # 80        - - AAT GAA GAT GAC TAT ATA TCA TAT TTT TCC TC - #A CTT TCT ACG ATT GAA           408                                                                        Asn Glu Asp Asp Tyr Ile Ser Tyr Phe Ser Se - #r Leu Ser Thr Ile Glu                             85 - #                 90 - #                 95               - - AAG GAT GTT AAA GAT AAC AAT AAA AAC GGG GC - #G GAC CTT ATT GGC TCA           456                                                                        Lys Asp Val Lys Asp Asn Asn Lys Asn Gly Al - #a Asp Leu Ile Gly Ser                        100      - #           105      - #           110                   - - ATA GAC GAG CCT AGT ACA ACA AAT CCA CCC GA - #A AAG CAT CAT GGA CAA           504                                                                        Ile Asp Glu Pro Ser Thr Thr Asn Pro Pro Gl - #u Lys His His Gly Gln                    115          - #       120          - #       125                       - - AAA TAT GTA TAT TCA GGG CTT TAT TAT ACT CC - #A TCG TGG AGT TTA AAC           552                                                                        Lys Tyr Val Tyr Ser Gly Leu Tyr Tyr Thr Pr - #o Ser Trp Ser Leu Asn                130              - #   135              - #   140                           - - GAT TCT AAA AAC AAG TTT TAT TTA GGT TAC TA - #T GGA TAT GCG TTT TAT           600                                                                        Asp Ser Lys Asn Lys Phe Tyr Leu Gly Tyr Ty - #r Gly Tyr Ala Phe Tyr            145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - TAT GGT AAT AAA ACT GCA ACA AAC TTG CCA GT - #A AAC GGT GTA GCT         AAA      648                                                                     Tyr Gly Asn Lys Thr Ala Thr Asn Leu Pro Va - #l Asn Gly Val Ala Lys                           165  - #               170  - #               175               - - TAC AAA GGA ACT TGG GAT TTC ATC ACT GCA AC - #T AAA AAT GGC AAA CGT           696                                                                        Tyr Lys Gly Thr Trp Asp Phe Ile Thr Ala Th - #r Lys Asn Gly Lys Arg                        180      - #           185      - #           190                   - - TAT CCT TTG TTA AGT AAT GGC AGT CAC GCT TA - #T TAT CGA CGT AGT GCA           744                                                                        Tyr Pro Leu Leu Ser Asn Gly Ser His Ala Ty - #r Tyr Arg Arg Ser Ala                    195          - #       200          - #       205                       - - ATT CCA GAA GAT ATT GAT TTA GAA AAT GAT TC - #A AAG AAT GGT GAT ATA           792                                                                        Ile Pro Glu Asp Ile Asp Leu Glu Asn Asp Se - #r Lys Asn Gly Asp Ile                210              - #   215              - #   220                           - - GGC TTA ATA AGT GAA TTT AGT GCA GAT TTT GG - #G ACT AAA AAA CTG ACA           840                                                                        Gly Leu Ile Ser Glu Phe Ser Ala Asp Phe Gl - #y Thr Lys Lys Leu Thr            225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - GGA CAA CTG TCT TAC ACC AAA AGA AAA ACT AA - #T AAT CAA CCA TAT         GAA      888                                                                     Gly Gln Leu Ser Tyr Thr Lys Arg Lys Thr As - #n Asn Gln Pro Tyr Glu                           245  - #               250  - #               255               - - AAG AAA AAA CTC TAT GAT ATA GAT GCC GAT AT - #T TAT AGT AAT AGA TTC           936                                                                        Lys Lys Lys Leu Tyr Asp Ile Asp Ala Asp Il - #e Tyr Ser Asn Arg Phe                        260      - #           265      - #           270                   - - AGG GGT ACA GTA AAG CCA ACC GAA AAA GAT TC - #T GAA GAA CAT CCC TTT           984                                                                        Arg Gly Thr Val Lys Pro Thr Glu Lys Asp Se - #r Glu Glu His Pro Phe                    275          - #       280          - #       285                       - - ACC AGC GAG GGA ACA TTA GAA GGT GGT TTT TA - #T GGG CCT AAT GCT GAA          1032                                                                        Thr Ser Glu Gly Thr Leu Glu Gly Gly Phe Ty - #r Gly Pro Asn Ala Glu                290              - #   295              - #   300                           - - GAA CTA GGG GGG AAA TTT TTA GCT ACG GAT AA - #C CGA GTT TTT GGG GTA          1080                                                                        Glu Leu Gly Gly Lys Phe Leu Ala Thr Asp As - #n Arg Val Phe Gly Val            305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - TTT AGT GCC AAA GAA ACG GAA GAA ACA AAA AA - #G GAA GCG TTA TCC         AAG     1128                                                                     Phe Ser Ala Lys Glu Thr Glu Glu Thr Lys Ly - #s Glu Ala Leu Ser Lys                           325  - #               330  - #               335               - - GAA ACC TTA ATT GAT GGC AAG CTA ATT ACT TT - #C TCT ACT AAA AAA ACC          1176                                                                        Glu Thr Leu Ile Asp Gly Lys Leu Ile Thr Ph - #e Ser Thr Lys Lys Thr                        340      - #           345      - #           350                   - - GAT GCA AAA ACC AAT GCA ACA ACC AGT ACC GC - #A GCT AAT ACA ACA ACC          1224                                                                        Asp Ala Lys Thr Asn Ala Thr Thr Ser Thr Al - #a Ala Asn Thr Thr Thr                    355          - #       360          - #       365                       - - GAT ACA ACC GCC AAT ACA ATA ACC GAT GAA AA - #A AAC TTT AAG ACG GAA          1272                                                                        Asp Thr Thr Ala Asn Thr Ile Thr Asp Glu Ly - #s Asn Phe Lys Thr Glu                370              - #   375              - #   380                           - - GAT ATA TCA AGT TTT GGT GAA GCT GAT TAT CT - #G TTA ATT GAC AAA TAT          1320                                                                        Asp Ile Ser Ser Phe Gly Glu Ala Asp Tyr Le - #u Leu Ile Asp Lys Tyr            385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - CCT ATT CCA CTT TTA CCT GAT AAA AAT ACT AA - #T GAT TTC ATA AGT         AGT     1368                                                                     Pro Ile Pro Leu Leu Pro Asp Lys Asn Thr As - #n Asp Phe Ile Ser Ser                           405  - #               410  - #               415               - - AAG CAT CAT ACT GTA GGA AAT AAA CGC TAT AA - #A GTG GAA GCA TGT TGC          1416                                                                        Lys His His Thr Val Gly Asn Lys Arg Tyr Ly - #s Val Glu Ala Cys Cys                        420      - #           425      - #           430                   - - AGT AAT CTA AGC TAT GTG AAA TTT GGT ATG TA - #T TAT GAA GAC CCA CTT          1464                                                                        Ser Asn Leu Ser Tyr Val Lys Phe Gly Met Ty - #r Tyr Glu Asp Pro Leu                    435          - #       440          - #       445                       - - AAA GAA AAA GAA ACA GAA ACA GAA ACA GAA AC - #A GAA AAA GAC AAA GAA          1512                                                                        Lys Glu Lys Glu Thr Glu Thr Glu Thr Glu Th - #r Glu Lys Asp Lys Glu                450              - #   455              - #   460                           - - AAA GAA AAA GAA AAA GAC AAA GAC AAA GAA AA - #A CAA ACG GCG GCA ACG          1560                                                                        Lys Glu Lys Glu Lys Asp Lys Asp Lys Glu Ly - #s Gln Thr Ala Ala Thr            465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - ACC AAC ACT TAT TAT CAA TTC TTA TTA GGT CA - #C CGT ACT CCC AAG         GAC     1608                                                                     Thr Asn Thr Tyr Tyr Gln Phe Leu Leu Gly Hi - #s Arg Thr Pro Lys Asp                           485  - #               490  - #               495               - - GAC ATA CCT AAA ACA GGA AGT GCA AAA TAT CA - #T GGT AGT TGG TTT GGT          1656                                                                        Asp Ile Pro Lys Thr Gly Ser Ala Lys Tyr Hi - #s Gly Ser Trp Phe Gly                        500      - #           505      - #           510                   - - TAT ATT ACT GAC GGT AAG ACA TCT TAC TCC CC - #C AGT GGT GAT AAG AAA          1704                                                                        Tyr Ile Thr Asp Gly Lys Thr Ser Tyr Ser Pr - #o Ser Gly Asp Lys Lys                    515          - #       520          - #       525                       - - CGC GAT AAA AAT GCT GTC GCC GAG TTT AAT GT - #T GAT TTT GCC GAG AAA          1752                                                                        Arg Asp Lys Asn Ala Val Ala Glu Phe Asn Va - #l Asp Phe Ala Glu Lys                530              - #   535              - #   540                           - - AAG CTA ACA GGC GAA TTA AAA CGA CAC GAT AC - #T GGA AAT CCC GTA TTT          1800                                                                        Lys Leu Thr Gly Glu Leu Lys Arg His Asp Th - #r Gly Asn Pro Val Phe            545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - AGT ATT GAG GCA AAC TTT AAT AAT AGT AGT AA - #T GCC TTC ACT GGT         ACA     1848                                                                     Ser Ile Glu Ala Asn Phe Asn Asn Ser Ser As - #n Ala Phe Thr Gly Thr                           565  - #               570  - #               575               - - GCA ACC GCA ACA AAT TTT GTA ATA GAT GGT AA - #A AAT AGT CAA AAT AAA          1896                                                                        Ala Thr Ala Thr Asn Phe Val Ile Asp Gly Ly - #s Asn Ser Gln Asn Lys                        580      - #           585      - #           590                   - - AAT ACC CCA ATT AAT ATT ACA ACT AAA GTA AA - #C GGG GCA TTT TAT GGA          1944                                                                        Asn Thr Pro Ile Asn Ile Thr Thr Lys Val As - #n Gly Ala Phe Tyr Gly                    595          - #       600          - #       605                       - - CCT AAG GCT TCT GAA TTA GGC GGT TAT TTC AC - #T TAT AAC GGA AAT TCT          1992                                                                        Pro Lys Ala Ser Glu Leu Gly Gly Tyr Phe Th - #r Tyr Asn Gly Asn Ser                610              - #   615              - #   620                           - - ACA GCT ACA AAT TCT GAA AGT TCC TCA ACC GT - #A TCT TCA TCA TCC AAT          2040                                                                        Thr Ala Thr Asn Ser Glu Ser Ser Ser Thr Va - #l Ser Ser Ser Ser Asn            625                 6 - #30                 6 - #35                 6 -       #40                                                                               - - TCA AAA AAT GCA AGA GCT GCA GTT GTC TTT GG - #T GCG AGA CAA CAA         GTA     2088                                                                     Ser Lys Asn Ala Arg Ala Ala Val Val Phe Gl - #y Ala Arg Gln Gln Val                           645  - #               650  - #               655               - - GAA ACA ACC AAA TAATGGAATA CTAAAA ATG ACT AAA - #AAA CCC TAT TTT            2137                                                                         Glu Thr Thr Lys            - #       Met Thr Lys Lys Pro Tyr P - #he                       660      - #                  - #           665                     - - CGC CTA AGT ATT ATT TCT TGT CTT TTA ATT TC - #A TGC TAT GTA AAA GCA          2185                                                                        Arg Leu Ser Ile Ile Ser Cys Leu Leu Ile Se - #r Cys Tyr Val Lys Ala                    670          - #       675          - #       680                       - - GAA ACT CAA AGT ATA AAA GAT ACA AAA GAA GC - #T ATA TCA TCT GAA GTG          2233                                                                        Glu Thr Gln Ser Ile Lys Asp Thr Lys Glu Al - #a Ile Ser Ser Glu Val                685              - #   690              - #   695                           - - GAC ACT CAA AGT ACA GAA GAT TCA GAA TTA GA - #A ACT ATC TCA GTC ACT          2281                                                                        Asp Thr Gln Ser Thr Glu Asp Ser Glu Leu Gl - #u Thr Ile Ser Val Thr            700                 7 - #05                 7 - #10                 7 -       #15                                                                               - - GCA GAA AAA ATA AGA GAT CGT AAA GAT AAT GA - #A GTA ACT GGA CTT         GGC     2329                                                                     Ala Glu Lys Ile Arg Asp Arg Lys Asp Asn Gl - #u Val Thr Gly Leu Gly                           720  - #               725  - #               730               - - AAA ATT ATC AAA ACT AGT GAA AGT ATC AGC CG - #A GAA CAA GTA TTA AAT          2377                                                                        Lys Ile Ile Lys Thr Ser Glu Ser Ile Ser Ar - #g Glu Gln Val Leu Asn                        735      - #           740      - #           745                   - - ATT CGT GAT CTA ACA CGC TAT GAT CCA GGG AT - #T TCA GTT GTA GAA CAA          2425                                                                        Ile Arg Asp Leu Thr Arg Tyr Asp Pro Gly Il - #e Ser Val Val Glu Gln                    750          - #       755          - #       760                       - - GGT CGC GGT GCA AGT TCT GGA TAT TCT ATT CG - #T GGT ATG GAC AGA AAT          2473                                                                        Gly Arg Gly Ala Ser Ser Gly Tyr Ser Ile Ar - #g Gly Met Asp Arg Asn                765              - #   770              - #   775                           - - AGA GTT GCT TTA TTA GTA GAT GGT TTA CCT CA - #A ACG CAA TCT TAT GTA          2521                                                                        Arg Val Ala Leu Leu Val Asp Gly Leu Pro Gl - #n Thr Gln Ser Tyr Val            780                 7 - #85                 7 - #90                 7 -       #95                                                                               - - GTG CAA AGC CCT TTA GTT GCT CGT TCA GGA TA - #T TCT GGC ACT GGT         GCA     2569                                                                     Val Gln Ser Pro Leu Val Ala Arg Ser Gly Ty - #r Ser Gly Thr Gly Ala                           800  - #               805  - #               810               - - ATT AAT GAA ATT GAA TAT GAA AAT GTA AAG GC - #C GTC GAA ATA AGC AAG          2617                                                                        Ile Asn Glu Ile Glu Tyr Glu Asn Val Lys Al - #a Val Glu Ile Ser Lys                        815      - #           820      - #           825                   - - GGG GGG AGT TCT TCT GAG TAT GGT AAT GGA GC - #A CTA GCT GGT TCT GTA          2665                                                                        Gly Gly Ser Ser Ser Glu Tyr Gly Asn Gly Al - #a Leu Ala Gly Ser Val                    830          - #       835          - #       840                       - - ACA TTT CAA AGC AAA TCA GCA GCC GAT ATC TT - #A GAA GGA GAC AAA TCA          2713                                                                        Thr Phe Gln Ser Lys Ser Ala Ala Asp Ile Le - #u Glu Gly Asp Lys Ser                845              - #   850              - #   855                           - - TGG GGA ATT CAA ACT AAA AAT GCT TAT TCA AG - #C AAA AAT AAA GGC TTT          2761                                                                        Trp Gly Ile Gln Thr Lys Asn Ala Tyr Ser Se - #r Lys Asn Lys Gly Phe            860                 8 - #65                 8 - #70                 8 -       #75                                                                               - - ACC CAT TCT TTA GCT GTA GCA GGA AAA CAA GG - #T GGA TTT GAA GGG         CTA     2809                                                                     Thr His Ser Leu Ala Val Ala Gly Lys Gln Gl - #y Gly Phe Glu Gly Leu                           880  - #               885  - #               890               - - GCC ATT TAC ACT CAA CGA AAT TCA ATT GAA AC - #C CAA GTC CAT AAA GAT          2857                                                                        Ala Ile Tyr Thr Gln Arg Asn Ser Ile Glu Th - #r Gln Val His Lys Asp                        895      - #           900      - #           905                   - - GCA TTA AAA GGC GTA CAA AGT TAT GAT CGA TT - #A ATC GCC ACA ACA GAT          2905                                                                        Ala Leu Lys Gly Val Gln Ser Tyr Asp Arg Le - #u Ile Ala Thr Thr Asp                    910          - #       915          - #       920                       - - AAA TCT TCA GGA TAC TTT GTG ATA CAA GGT GA - #G TGT CCA AAT GGT GAT          2953                                                                        Lys Ser Ser Gly Tyr Phe Val Ile Gln Gly Gl - #u Cys Pro Asn Gly Asp                925              - #   930              - #   935                           - - GAC AAG TGT GCA GCC AAG CCA CCT GCG ACT TT - #A TCC ACC CAA AGC GAA          3001                                                                        Asp Lys Cys Ala Ala Lys Pro Pro Ala Thr Le - #u Ser Thr Gln Ser Glu            940                 9 - #45                 9 - #50                 9 -       #55                                                                               - - ACC GTA AGC GTT TCA GAT TAT ACG GGG GCT AA - #C CGT ATC AAA CCT         AAT     3049                                                                     Thr Val Ser Val Ser Asp Tyr Thr Gly Ala As - #n Arg Ile Lys Pro Asn                           960  - #               965  - #               970               - - CCA ATG AAA TAT GAA AGC CAG TCT TGG TTT TT - #A AGA GGA GGG TAT CAT          3097                                                                        Pro Met Lys Tyr Glu Ser Gln Ser Trp Phe Le - #u Arg Gly Gly Tyr His                        975      - #           980      - #           985                   - - TTT TCT GAA CAA CAT TAT ATT GGT GGT ATT TT - #T GAA TTC ACA CAA CAA          3145                                                                        Phe Ser Glu Gln His Tyr Ile Gly Gly Ile Ph - #e Glu Phe Thr Gln Gln                    990          - #       995          - #       1000                      - - AAA TTT GAT ATC CGT GAT ATG ACA TTT CCC GC - #T TAT TTA AGC CCA ACA          3193                                                                        Lys Phe Asp Ile Arg Asp Met Thr Phe Pro Al - #a Tyr Leu Ser Pro Thr                1005             - #   1010              - #  1015                          - - GAA AGA CGG GAT GAT AGT AGT CGT TCT TTT TA - #T CCA ATG CAA GAT CAT          3241                                                                        Glu Arg Arg Asp Asp Ser Ser Arg Ser Phe Ty - #r Pro Met Gln Asp His            1020                1025 - #                1030 - #               1035         - - GGT GCA TAT CAA CAT ATT GAG GAT GGC AGA GG - #C GTT AAA TAT GCA AGT          3289                                                                        Gly Ala Tyr Gln His Ile Glu Asp Gly Arg Gl - #y Val Lys Tyr Ala Ser                            1040 - #               1045  - #              1050              - - GGG CTT TAT TTC GAT GAA CAC CAT AGA AAA CA - #G CGT GTA GGT ATT GAA          3337                                                                        Gly Leu Tyr Phe Asp Glu His His Arg Lys Gl - #n Arg Val Gly Ile Glu                        1055     - #           1060      - #          1065                  - - TAT ATT TAC GAA AAT AAG AAC AAA GCG GGC AT - #C ATT GAC AAA GCA GTG          3385                                                                        Tyr Ile Tyr Glu Asn Lys Asn Lys Ala Gly Il - #e Ile Asp Lys Ala Val                    1070         - #       1075          - #      1080                      - - TTA AGT GCT AAT CAA CAA AAC ATC ATA CTT GA - #C AGT TAT ATG CGA CAT          3433                                                                        Leu Ser Ala Asn Gln Gln Asn Ile Ile Leu As - #p Ser Tyr Met Arg His                1085             - #   1090              - #  1095                          - - ACG CAT TGC AGT CTT TAT CCT AAT CCA AGT AA - #G AAT TGC CGC CCA ACA          3481                                                                        Thr His Cys Ser Leu Tyr Pro Asn Pro Ser Ly - #s Asn Cys Arg Pro Thr            1100                1105 - #                1110 - #               1115         - - CTT GAT AAA CCT TAT TCA TAC TAT CGT TCT GA - #T AGA AAT GTT TAT AAA          3529                                                                        Leu Asp Lys Pro Tyr Ser Tyr Tyr Arg Ser As - #p Arg Asn Val Tyr Lys                            1120 - #               1125  - #              1130              - - GAA AAA CAT AAT ATG TTG CAA TTG AAT TTA GA - #G AAA AAA ATT CAA CAA          3577                                                                        Glu Lys His Asn Met Leu Gln Leu Asn Leu Gl - #u Lys Lys Ile Gln Gln                        1135     - #           1140      - #          1145                  - - AAT TGG CTT ACT CAT CAA ATT GTC TTC AAT CT - #T GGT TTT GAT GAC TTT          3625                                                                        Asn Trp Leu Thr His Gln Ile Val Phe Asn Le - #u Gly Phe Asp Asp Phe                    1150         - #       1155          - #      1160                      - - ACT TCA GCG CTT CAG CAT AAA GAT TAT TTA AC - #T CGA CGT GTT ATC GCT          3673                                                                        Thr Ser Ala Leu Gln His Lys Asp Tyr Leu Th - #r Arg Arg Val Ile Ala                1165             - #   1170              - #  1175                          - - ACG GCA GAT AGT ATT CCA AGG AAA CCT GGT GA - #A ACT GGT AAA CCA AGA          3721                                                                        Thr Ala Asp Ser Ile Pro Arg Lys Pro Gly Gl - #u Thr Gly Lys Pro Arg            1180                1185 - #                1190 - #               1195         - - AAT GGT TTG CAA TCA CAA CCT TAC TTA TAC CC - #A AAA CCA GAG CCA TAT          3769                                                                        Asn Gly Leu Gln Ser Gln Pro Tyr Leu Tyr Pr - #o Lys Pro Glu Pro Tyr                            1200 - #               1205  - #              1210              - - TTT GCA GGA CAA GAT CAT TGT AAT TAT CAA GG - #T AGC TCC TCT AAT TAC          3817                                                                        Phe Ala Gly Gln Asp His Cys Asn Tyr Gln Gl - #y Ser Ser Ser Asn Tyr                        1215     - #           1220      - #          1225                  - - AGA GAC TGT AAA GTG CGG TTA ATT AAA GGG AA - #A AAT TAT TAT TTC GCA          3865                                                                        Arg Asp Cys Lys Val Arg Leu Ile Lys Gly Ly - #s Asn Tyr Tyr Phe Ala                    1230         - #       1235          - #      1240                      - - GCA CGC AAT AAT ATG GCA TTA GGG AAA TAC GT - #T GAT TTA GGT TTA GGT          3913                                                                        Ala Arg Asn Asn Met Ala Leu Gly Lys Tyr Va - #l Asp Leu Gly Leu Gly                1245             - #   1250              - #  1255                          - - ATT CGG TAT GAC GTA TCT CGT ACA AAA GCT AA - #T GAA TCA ACT ATT AGT          3961                                                                        Ile Arg Tyr Asp Val Ser Arg Thr Lys Ala As - #n Glu Ser Thr Ile Ser            1260                1265 - #                1270 - #               1275         - - GTT GGT AAA TTT AAA AAT TTC TCT TGG AAT AC - #T GGT ATT GTC ATA AAA          4009                                                                        Val Gly Lys Phe Lys Asn Phe Ser Trp Asn Th - #r Gly Ile Val Ile Lys                            1280 - #               1285  - #              1290              - - CCA ACG GAA TGG CTT GAT CTT TCT TAT CGC CT - #T TCT ACT GGA TTT AGA          4057                                                                        Pro Thr Glu Trp Leu Asp Leu Ser Tyr Arg Le - #u Ser Thr Gly Phe Arg                        1295     - #           1300      - #          1305                  - - AAT CCT AGT TTT TCT GAA ATG TAT GGT TGG CG - #G TAT GGT GGC AAG AAT          4105                                                                        Asn Pro Ser Phe Ser Glu Met Tyr Gly Trp Ar - #g Tyr Gly Gly Lys Asn                    1310         - #       1315          - #      1320                      - - GAC GAG GTT TAT GTA GGT AAA TTT AAG CCT GA - #A ACA TCT CGT AAC CAA          4153                                                                        Asp Glu Val Tyr Val Gly Lys Phe Lys Pro Gl - #u Thr Ser Arg Asn Gln                1325             - #   1330              - #  1335                          - - GAG TTT GGT CTC GCT CTA AAA GGG GAT TTT GG - #T AAT ATT GAG ATC AGT          4201                                                                        Glu Phe Gly Leu Ala Leu Lys Gly Asp Phe Gl - #y Asn Ile Glu Ile Ser            1340                1345 - #                1350 - #               1355         - - CAT TTT AGT AAT GCT TAT CGA AAT CTT ATC GC - #C TTT GCT GAA GAA CTT          4249                                                                        His Phe Ser Asn Ala Tyr Arg Asn Leu Ile Al - #a Phe Ala Glu Glu Leu                            1360 - #               1365  - #              1370              - - AGT AAA AAT GGA ACT GGA AAG GGC AAT TAT GG - #A TAT CAT AAT GCA CAA          4297                                                                        Ser Lys Asn Gly Thr Gly Lys Gly Asn Tyr Gl - #y Tyr His Asn Ala Gln                        1375     - #           1380      - #          1385                  - - AAT GCA AAA TTA GTT GGC GTA AAT ATA ACT GC - #A CAA TTA GAT TTT AAT          4345                                                                        Asn Ala Lys Leu Val Gly Val Asn Ile Thr Al - #a Gln Leu Asp Phe Asn                    1390         - #       1395          - #      1400                      - - GGT TTA TGG AAA CGT ATT CCC TAC GGT TGG TA - #T GCA ACA TTT GCT TAT          4393                                                                        Gly Leu Trp Lys Arg Ile Pro Tyr Gly Trp Ty - #r Ala Thr Phe Ala Tyr                1405             - #   1410              - #  1415                          - - AAC CAA GTA AAA GTT AAA GAT CAA AAA ATC AA - #T GCT GGT TTA GCC TCC          4441                                                                        Asn Gln Val Lys Val Lys Asp Gln Lys Ile As - #n Ala Gly Leu Ala Ser            1420                1425 - #                1430 - #               1435         - - GTA AGC AGT TAT TTA TTT GAT GCC ATT CAG CC - #C AGC CGT TAT ATC ATT          4489                                                                        Val Ser Ser Tyr Leu Phe Asp Ala Ile Gln Pr - #o Ser Arg Tyr Ile Ile                            1440 - #               1445  - #              1450              - - GGT TTA GGC TAT GAT CAT CCA AGT AAT ACT TG - #G GGA ATT AAT ACA ATG          4537                                                                        Gly Leu Gly Tyr Asp His Pro Ser Asn Thr Tr - #p Gly Ile Asn Thr Met                        1455     - #           1460      - #          1465                  - - TTT ACT CAA TCA AAA GCA AAA TCT CAA AAT GA - #A TTG CTA GGA AAA CGT          4585                                                                        Phe Thr Gln Ser Lys Ala Lys Ser Gln Asn Gl - #u Leu Leu Gly Lys Arg                    1470         - #       1475          - #      1480                      - - GCA TTA GGT AAC AAT TCA AGG GAT GTA AAA TC - #A ACA AGA AAA CTT ACT          4633                                                                        Ala Leu Gly Asn Asn Ser Arg Asp Val Lys Se - #r Thr Arg Lys Leu Thr                1485             - #   1490              - #  1495                          - - CGG GCA TGG CAT ATC TTA GAT GTA TCG GGT TA - #T TAC ATG GCG AAT AAA          4681                                                                        Arg Ala Trp His Ile Leu Asp Val Ser Gly Ty - #r Tyr Met Ala Asn Lys            1500                1505 - #                1510 - #               1515         - - AAT ATT ATG CTT CGA TTA GGG ATA TAT AAT TT - #A TTC AAC TAT CGC TAT          4729                                                                        Asn Ile Met Leu Arg Leu Gly Ile Tyr Asn Le - #u Phe Asn Tyr Arg Tyr                            1520 - #               1525  - #              1530              - - GTT ACT TGG GAA GCG GTG CGT CAA ACA GCA CA - #A GGT GCG GTC AAT CAA          4777                                                                        Val Thr Trp Glu Ala Val Arg Gln Thr Ala Gl - #n Gly Ala Val Asn Gln                        1535     - #           1540      - #          1545                  - - CAT CAA AAT GTT GGT AGC TAT ACT CGC TAC GC - #A GCA TCA GGA CGA AAC          4825                                                                        His Gln Asn Val Gly Ser Tyr Thr Arg Tyr Al - #a Ala Ser Gly Arg Asn                    1550         - #       1555          - #      1560                      - - TAT ACC TTA ACA TTA GAA ATG AAA TTC TAAATTAAA - #A TGCGCCAGAT                4872                                                                        Tyr Thr Leu Thr Leu Glu Met Lys Phe                                                1565             - #   1570                                                 - - GGACTAGATA TGCTATATCT ATACCTTACT GGCGCATCTT TTTCTGTTCT AT -              #AATCTGCT   4932                                                                  - - TAAGTGAAAA ACCAAACTTG GATTTTTTAC AAGATCTTTT CACACATTTA TT -             #GTAAAATC   4992                                                                  - - TCCGACAATT TTGACCG             - #                  - #                       - # 5009                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:4:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 5099 base - #pairs                                                 (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: double                                                       (D) TOPOLOGY: linear                                                  - -     (ix) FEATURE:                                                                   (A) NAME/KEY: CDS                                                              (B) LOCATION: join(160..21 - #21, 2152..4890)                         - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:4:                                - - AAAATTCGGT AATGATAACC CTATAAATGA TAAGAGAGAA AGTTGTTTTA CG -              #CCATTTTT     60                                                                  - - CATATTTTAT CCATGAACTT AAAAAATTCT AAGTTGACAT TATTACAAAA AA -             #AGAACAAT    120                                                                  - - AATGCGAATT ATTATCAATT TTGTATAAGT ATTAATTCT ATG AAA TCT - # GTA CCT            174                                                                                         - #                  - #       Met Lys Ser Val Pro                             - #                  - #         1         - #      5         - - CTT ATC ACT GGT GGA CTT TCC TTT TTA CTA AG - #C GCT TGT AGC GGG GGA           222                                                                        Leu Ile Thr Gly Gly Leu Ser Phe Leu Leu Se - #r Ala Cys Ser Gly Gly                             10 - #                 15 - #                 20               - - GGT GGT TCT TTT GAT GTA GAT GAC GTC TCT AA - #T CCC TCC TCT TCT AAA           270                                                                        Gly Gly Ser Phe Asp Val Asp Asp Val Ser As - #n Pro Ser Ser Ser Lys                         25     - #             30     - #             35                   - - CCA CGT TAT CAA GAC GAT ACC TCG AAT CAA AG - #A ACA AAA TCT GAT TTG           318                                                                        Pro Arg Tyr Gln Asp Asp Thr Ser Asn Gln Ar - #g Thr Lys Ser Asp Leu                     40         - #         45         - #         50                       - - GAA AAG TTG TTC ATT CCT TCT TTA GGG GGA GG - #G ATG AAG TTA GTG GCT           366                                                                        Glu Lys Leu Phe Ile Pro Ser Leu Gly Gly Gl - #y Met Lys Leu Val Ala                 55             - #     60             - #     65                           - - CAA AAT TTT ATT GGT GCT AGA GAA CCT AGT TT - #C TTA AAT GAA GAT GGC           414                                                                        Gln Asn Phe Ile Gly Ala Arg Glu Pro Ser Ph - #e Leu Asn Glu Asp Gly             70                 - # 75                 - # 80                 - # 85        - - TAT ATG ATA TTT TCC TCA CTT TCT ACG ATT GA - #A GAG GAT GTT GAA AAA           462                                                                        Tyr Met Ile Phe Ser Ser Leu Ser Thr Ile Gl - #u Glu Asp Val Glu Lys                             90 - #                 95 - #                100               - - GTT AAA AAT AAC AAT AAA AAC GGG GGG AGG CT - #T ATT GGC TCA ATT GAG           510                                                                        Val Lys Asn Asn Asn Lys Asn Gly Gly Arg Le - #u Ile Gly Ser Ile Glu                        105      - #           110      - #           115                   - - GAA CCT AAT GGA ACA TCA CAA AAT TCT AAT TC - #A CAA GAA TAC GTT TAT           558                                                                        Glu Pro Asn Gly Thr Ser Gln Asn Ser Asn Se - #r Gln Glu Tyr Val Tyr                    120          - #       125          - #       130                       - - TCT GGT TTG TAT TAT ATC GAT AGT TGG CGT GA - #T TAT AAG AAG GAA GAG           606                                                                        Ser Gly Leu Tyr Tyr Ile Asp Ser Trp Arg As - #p Tyr Lys Lys Glu Glu                135              - #   140              - #   145                           - - CAA AAA GCT TAT ACT GGC TAT TAT GGT TAT GC - #A TTT TAT TAT GGT AAT           654                                                                        Gln Lys Ala Tyr Thr Gly Tyr Tyr Gly Tyr Al - #a Phe Tyr Tyr Gly Asn            150                 1 - #55                 1 - #60                 1 -       #65                                                                               - - GAA ACT GCA AAA AAC TTG CCA GTA AAA GGT GT - #A GCT AAA TAC AAA         GGA      702                                                                     Glu Thr Ala Lys Asn Leu Pro Val Lys Gly Va - #l Ala Lys Tyr Lys Gly                           170  - #               175  - #               180               - - ACG TGG AAC TTC ATC ACT GCA ACT GAA AAT GG - #C AAA CGT TAT TCT TTG           750                                                                        Thr Trp Asn Phe Ile Thr Ala Thr Glu Asn Gl - #y Lys Arg Tyr Ser Leu                        185      - #           190      - #           195                   - - TTC AGT AAT TCT ATC GGT CAA GCT TAT TCC AG - #A CGC AGC GCT ATT TCA           798                                                                        Phe Ser Asn Ser Ile Gly Gln Ala Tyr Ser Ar - #g Arg Ser Ala Ile Ser                    200          - #       205          - #       210                       - - GAA GAT ATC TAT AAT TTA GAA AAC GGT GAC GC - #G GGC TTA ATA AGT GAA           846                                                                        Glu Asp Ile Tyr Asn Leu Glu Asn Gly Asp Al - #a Gly Leu Ile Ser Glu                215              - #   220              - #   225                           - - TTT AGT GTA GAT TTT GGT AAG AAA GAG CTC AC - #T GGA GAA CTT TAT TAT           894                                                                        Phe Ser Val Asp Phe Gly Lys Lys Glu Leu Th - #r Gly Glu Leu Tyr Tyr            230                 2 - #35                 2 - #40                 2 -       #45                                                                               - - AAT GAA AGG AAA ACA AGT GTT AAT GAA TCA CA - #A AAT ACA ACA CAT         AAA      942                                                                     Asn Glu Arg Lys Thr Ser Val Asn Glu Ser Gl - #n Asn Thr Thr His Lys                           250  - #               255  - #               260               - - CTC TAC ACT CTA GAA GCT AAA GTG TAT AGC AA - #C CGA TTC AGA GGT AAA           990                                                                        Leu Tyr Thr Leu Glu Ala Lys Val Tyr Ser As - #n Arg Phe Arg Gly Lys                        265      - #           270      - #           275                   - - GTA AAG CCA ACC AAA ACA AAG TCT GAA GAT CA - #T CCC TTT ACC AGC GAG          1038                                                                        Val Lys Pro Thr Lys Thr Lys Ser Glu Asp Hi - #s Pro Phe Thr Ser Glu                    280          - #       285          - #       290                       - - GGA ACA TTA GAA GGT GGT TTT TAT GGG CCT AA - #T GCT GAA GAA CTA GGG          1086                                                                        Gly Thr Leu Glu Gly Gly Phe Tyr Gly Pro As - #n Ala Glu Glu Leu Gly                295              - #   300              - #   305                           - - GGA AAG TTT TTA GCT AAC GAC GAA AAA GTT TT - #T GGG GTA TTT AGT GCC          1134                                                                        Gly Lys Phe Leu Ala Asn Asp Glu Lys Val Ph - #e Gly Val Phe Ser Ala            310                 3 - #15                 3 - #20                 3 -       #25                                                                               - - AAA GAA GAC CCA CAA AAC CCA GAA AAC CAA AA - #A TTA TCC ACA GAA         ACC     1182                                                                     Lys Glu Asp Pro Gln Asn Pro Glu Asn Gln Ly - #s Leu Ser Thr Glu Thr                           330  - #               335  - #               340               - - TTA ATT GAT GGC AAG CTA ATT ACT TTT AAA AG - #A ACT GAT GCA ACA ACC          1230                                                                        Leu Ile Asp Gly Lys Leu Ile Thr Phe Lys Ar - #g Thr Asp Ala Thr Thr                        345      - #           350      - #           355                   - - AAT GCA ACA ACC GAT GCA AAA ACC AGT GCA AC - #A ACC GAT GCA ACC AGT          1278                                                                        Asn Ala Thr Thr Asp Ala Lys Thr Ser Ala Th - #r Thr Asp Ala Thr Ser                    360          - #       365          - #       370                       - - ACA ACA GCC AAT AAA AAA ACC GAT GCA GAA AA - #C TTT AAG ACG GAA GAT          1326                                                                        Thr Thr Ala Asn Lys Lys Thr Asp Ala Glu As - #n Phe Lys Thr Glu Asp                375              - #   380              - #   385                           - - ATA CCA AGT TTT GGT GAA GCT GAT TAC CTT TT - #A ATT GGC AAT CAG CCT          1374                                                                        Ile Pro Ser Phe Gly Glu Ala Asp Tyr Leu Le - #u Ile Gly Asn Gln Pro            390                 3 - #95                 4 - #00                 4 -       #05                                                                               - - ATT CCT CTT TTA CCT GAA AAA AAT ACT GAT GA - #T TTC ATA AGT AGT         AAG     1422                                                                     Ile Pro Leu Leu Pro Glu Lys Asn Thr Asp As - #p Phe Ile Ser Ser Lys                           410  - #               415  - #               420               - - CAC CAT ACG GTA GGA GGT AAA ACC TAT AAA GT - #A GAA GCA TGT TGC AAG          1470                                                                        His His Thr Val Gly Gly Lys Thr Tyr Lys Va - #l Glu Ala Cys Cys Lys                        425      - #           430      - #           435                   - - AAT CTA AGC TAT GTG AAA TTT GGT ATG TAT TA - #T GAG GAT AAA GAT AAG          1518                                                                        Asn Leu Ser Tyr Val Lys Phe Gly Met Tyr Ty - #r Glu Asp Lys Asp Lys                    440          - #       445          - #       450                       - - GAC AAC AAA AAT GAA ACA GAC AAA GAA AAA GG - #C AAA GAA AAA CCA ACG          1566                                                                        Asp Asn Lys Asn Glu Thr Asp Lys Glu Lys Gl - #y Lys Glu Lys Pro Thr                455              - #   460              - #   465                           - - ACG ACA ACA TCT ATC AAC ACT TAT TAT CAA TT - #C TTA TTA GGT CTC CGT          1614                                                                        Thr Thr Thr Ser Ile Asn Thr Tyr Tyr Gln Ph - #e Leu Leu Gly Leu Arg            470                 4 - #75                 4 - #80                 4 -       #85                                                                               - - ACT CCC AAG GAC GAA ATA CCT AAA GAA GGA AG - #T GCA AAA TAT CAT         GGT     1662                                                                     Thr Pro Lys Asp Glu Ile Pro Lys Glu Gly Se - #r Ala Lys Tyr His Gly                           490  - #               495  - #               500               - - AAT TGG TTT GGT TAT ATT AGT GAT GGC GAG AC - #A TCT TAC TCC GCC AGT          1710                                                                        Asn Trp Phe Gly Tyr Ile Ser Asp Gly Glu Th - #r Ser Tyr Ser Ala Ser                        505      - #           510      - #           515                   - - GGT GAT AAG GAA CGC AGT AAA AAT GCT GTC GC - #C GAG TTT GAT GTA AGT          1758                                                                        Gly Asp Lys Glu Arg Ser Lys Asn Ala Val Al - #a Glu Phe Asp Val Ser                    520          - #       525          - #       530                       - - TTT GCC AAT AAA ACA TTA ACA GGC GAA TTA AA - #A CGA CAC GAT AAT GGA          1806                                                                        Phe Ala Asn Lys Thr Leu Thr Gly Glu Leu Ly - #s Arg His Asp Asn Gly                535              - #   540              - #   545                           - - AAT ACC GTA TTT AAA ATT AAT GCA GAA TTA AA - #T GGT AGT AAT GAC TTC          1854                                                                        Asn Thr Val Phe Lys Ile Asn Ala Glu Leu As - #n Gly Ser Asn Asp Phe            550                 5 - #55                 5 - #60                 5 -       #65                                                                               - - ACT GGT ACA GCA ACC GCA ACA AAT TTT GTA AT - #A GAT GGT AAC AAT         AGT     1902                                                                     Thr Gly Thr Ala Thr Ala Thr Asn Phe Val Il - #e Asp Gly Asn Asn Ser                           570  - #               575  - #               580               - - CAA ACT TCA AAT GCC AAA ATT AAT ATT ACA AC - #T AAA GTA AAT GGG GCA          1950                                                                        Gln Thr Ser Asn Ala Lys Ile Asn Ile Thr Th - #r Lys Val Asn Gly Ala                        585      - #           590      - #           595                   - - TTT TAT GGA CCT AAG GCT TCT GAA TTA GGA GG - #G TAT TTC ACC TAT AAC          1998                                                                        Phe Tyr Gly Pro Lys Ala Ser Glu Leu Gly Gl - #y Tyr Phe Thr Tyr Asn                    600          - #       605          - #       610                       - - GGA AAA AAT CCT ACA GCT ACA AAT TCT GAA AG - #T TCC TCA ACC GTA CCT          2046                                                                        Gly Lys Asn Pro Thr Ala Thr Asn Ser Glu Se - #r Ser Ser Thr Val Pro                615              - #   620              - #   625                           - - TCA CCA CCC AAT TCA CCA AAT GCA AGC GCT GC - #A GTT GTC TTT GGT GCT          2094                                                                        Ser Pro Pro Asn Ser Pro Asn Ala Ser Ala Al - #a Val Val Phe Gly Ala            630                 6 - #35                 6 - #40                 6 -       #45                                                                               - - AAA AAA CAA GTA GAA ACA ACC AAC AAG TAAAAACAA - #C CAAGTAATGG                2141                                                                       Lys Lys Gln Val Glu Thr Thr Asn Lys                                                            650                                                             - - AATACTAAAA ATG ACT AAA AAA CCC TAT TTT CGC CT - #A AGT ATT ATT TCT           2190                                                                         - -            Met Thr Lys Lys - #Pro Tyr Phe Arg Leu Ser Ile Ile Ser                    655       - #          660       - #          665                    - - TGT CTT TTA ATT TCA TGC TAT GTA AAA GCA GA - #A ACT CAA AGT ATA AAA          2238                                                                        Cys Leu Leu Ile Ser Cys Tyr Val Lys Ala Gl - #u Thr Gln Ser Ile Lys                    670          - #       675          - #       680                       - - GAT ACA AAA GAA GCT ATA TCA TCT GAA GTG GA - #C ACT CAA AGT ACA GAA          2286                                                                        Asp Thr Lys Glu Ala Ile Ser Ser Glu Val As - #p Thr Gln Ser Thr Glu                685              - #   690              - #   695                           - - GAT TCA GAA TTA GAA ACT ATC TCA GTC ACT GC - #A GAA AAA ATA AGA GAT          2334                                                                        Asp Ser Glu Leu Glu Thr Ile Ser Val Thr Al - #a Glu Lys Ile Arg Asp            700                 7 - #05                 7 - #10                 7 -       #15                                                                               - - CGT AAA GAT AAT GAA GTA ACT GGA CTT GGC AA - #A ATT ATC AAA ACT         AGT     2382                                                                     Arg Lys Asp Asn Glu Val Thr Gly Leu Gly Ly - #s Ile Ile Lys Thr Ser                           720  - #               725  - #               730               - - GAA AGT ATC AGC CGA GAA CAA GTA TTA AAT AT - #T CGT GAT CTA ACA CGC          2430                                                                        Glu Ser Ile Ser Arg Glu Gln Val Leu Asn Il - #e Arg Asp Leu Thr Arg                        735      - #           740      - #           745                   - - TAT GAT CCA GGC ATT TCA GTT GTA GAA CAA GG - #C CGT GGT GCA AGT TCT          2478                                                                        Tyr Asp Pro Gly Ile Ser Val Val Glu Gln Gl - #y Arg Gly Ala Ser Ser                    750          - #       755          - #       760                       - - GGA TAT TCT ATT CGT GGT ATG GAC AGA AAT AG - #A GTT GCT TTA TTA GTA          2526                                                                        Gly Tyr Ser Ile Arg Gly Met Asp Arg Asn Ar - #g Val Ala Leu Leu Val                765              - #   770              - #   775                           - - GAT GGT TTA CCT CAA ACG CAA TCT TAT GTA GT - #G CAA AGC CCT TTA GTT          2574                                                                        Asp Gly Leu Pro Gln Thr Gln Ser Tyr Val Va - #l Gln Ser Pro Leu Val            780                 7 - #85                 7 - #90                 7 -       #95                                                                               - - GCT CGT TCA GGA TAT TCT GGC ACT GGT GCA AT - #T AAT GAA ATT GAA         TAT     2622                                                                     Ala Arg Ser Gly Tyr Ser Gly Thr Gly Ala Il - #e Asn Glu Ile Glu Tyr                           800  - #               805  - #               810               - - GAA AAT GTA AAG GCC GTC GAA ATA AGC AAG GG - #G GGG AGT TCT TCT GAG          2670                                                                        Glu Asn Val Lys Ala Val Glu Ile Ser Lys Gl - #y Gly Ser Ser Ser Glu                        815      - #           820      - #           825                   - - TAT GGT AAT GGA GCA CTA GCT GGT TCT GTA AC - #A TTT CAA AGC AAA TCA          2718                                                                        Tyr Gly Asn Gly Ala Leu Ala Gly Ser Val Th - #r Phe Gln Ser Lys Ser                    830          - #       835          - #       840                       - - GCA GCC GAT ATC TTA GAA GGA GAC AAA TCA TG - #G GGA ATT CAA ACT AAA          2766                                                                        Ala Ala Asp Ile Leu Glu Gly Asp Lys Ser Tr - #p Gly Ile Gln Thr Lys                845              - #   850              - #   855                           - - AAT GCT TAT TCA AGC AAA AAT AAA GGC TTT AC - #C CAT TCT TTA GCT GTA          2814                                                                        Asn Ala Tyr Ser Ser Lys Asn Lys Gly Phe Th - #r His Ser Leu Ala Val            860                 8 - #65                 8 - #70                 8 -       #75                                                                               - - GCT GGA AAA CAA GGG GGA TTT GAC GGG GTC GC - #C ATT TAT ACT CAA         CGA     2862                                                                     Ala Gly Lys Gln Gly Gly Phe Asp Gly Val Al - #a Ile Tyr Thr Gln Arg                           880  - #               885  - #               890               - - AAT TCA ATT GAA ACC CAA GTC CAT AAA GAT GC - #A TTA AAA GGC GTA CAA          2910                                                                        Asn Ser Ile Glu Thr Gln Val His Lys Asp Al - #a Leu Lys Gly Val Gln                        895      - #           900      - #           905                   - - AGT TAT CAT CGA TTA ATC GCC AAA CCA GAG GA - #T CAA TCT GCA TAC TTT          2958                                                                        Ser Tyr His Arg Leu Ile Ala Lys Pro Glu As - #p Gln Ser Ala Tyr Phe                    910          - #       915          - #       920                       - - GTG ATG CAA GAT GAG TGT CCA AAG CCA GAT GA - #T TAT AAC AGT TGT TTA          3006                                                                        Val Met Gln Asp Glu Cys Pro Lys Pro Asp As - #p Tyr Asn Ser Cys Leu                925              - #   930              - #   935                           - - CCT TTC GCC AAA CGA CCT GCG ATT TTA TCC TC - #C CAA AGA GAA ACC GTA          3054                                                                        Pro Phe Ala Lys Arg Pro Ala Ile Leu Ser Se - #r Gln Arg Glu Thr Val            940                 9 - #45                 9 - #50                 9 -       #55                                                                               - - AGC GTT TCA GAT TAT ACG GGG GCT AAC CGT AT - #C AAA CCT AAT CCA         ATG     3102                                                                     Ser Val Ser Asp Tyr Thr Gly Ala Asn Arg Il - #e Lys Pro Asn Pro Met                           960  - #               965  - #               970               - - AAA TAT GAA AGC CAG TCT TGG TTT TTA AGA GG - #A GGG TAT CAT TTT TCT          3150                                                                        Lys Tyr Glu Ser Gln Ser Trp Phe Leu Arg Gl - #y Gly Tyr His Phe Ser                        975      - #           980      - #           985                   - - GAA CAA CAT TAT ATT GGT GGT ATT TTT GAA TT - #C ACA CAA CAA AAA TTT          3198                                                                        Glu Gln His Tyr Ile Gly Gly Ile Phe Glu Ph - #e Thr Gln Gln Lys Phe                    990          - #       995          - #       1000                      - - GAT ATC CGT GAT ATG ACA TTT CCC GCT TAT TT - #A AGA TCA ACA GAA AAA          3246                                                                        Asp Ile Arg Asp Met Thr Phe Pro Ala Tyr Le - #u Arg Ser Thr Glu Lys                1005             - #   1010              - #  1015                          - - CGG GAT GAT AGC AGT GGC TCT TTT TAT CCA AA - #G CAA GAT TAT GGT GCA          3294                                                                        Arg Asp Asp Ser Ser Gly Ser Phe Tyr Pro Ly - #s Gln Asp Tyr Gly Ala            1020                1025 - #                1030 - #               1035         - - TAT CAA CGT ATT GAG GAT GGC CGA GGC GTT AA - #C TAT GCA AGT GGG CTT          3342                                                                        Tyr Gln Arg Ile Glu Asp Gly Arg Gly Val As - #n Tyr Ala Ser Gly Leu                            1040 - #               1045  - #              1050              - - TAT TTC GAT GAA CAC CAT AGA AAA CAG CGT GT - #A GGT ATT GAA TAT ATT          3390                                                                        Tyr Phe Asp Glu His His Arg Lys Gln Arg Va - #l Gly Ile Glu Tyr Ile                        1055     - #           1060      - #          1065                  - - TAC GAA AAT AAG AAC AAA GCG GGC ATC ATT GA - #C AAA GCA GTG TTA AGT          3438                                                                        Tyr Glu Asn Lys Asn Lys Ala Gly Ile Ile As - #p Lys Ala Val Leu Ser                    1070         - #       1075          - #      1080                      - - GCT AAT CAA CAA AAC ATC ATA CTT GAC AGT TA - #T ATG CAA CAT ACG CAT          3486                                                                        Ala Asn Gln Gln Asn Ile Ile Leu Asp Ser Ty - #r Met Gln His Thr His                1085             - #   1090              - #  1095                          - - TGC AGT CTT TAT CCT AAT CCA AGT AAG AAT TG - #C CGC CCA ACA CGT GAT          3534                                                                        Cys Ser Leu Tyr Pro Asn Pro Ser Lys Asn Cy - #s Arg Pro Thr Arg Asp            1100                1105 - #                1110 - #               1115         - - AAA CCT TAT TCA TAC TAT CAT TCT GAT AGA AA - #T GTT TAT AAA GAA AAA          3582                                                                        Lys Pro Tyr Ser Tyr Tyr His Ser Asp Arg As - #n Val Tyr Lys Glu Lys                            1120 - #               1125  - #              1130              - - CAT AAT ATG TTG CAA TTG AAT TTA GAG AAA AA - #A ATT CAA CAA AAT TGG          3630                                                                        His Asn Met Leu Gln Leu Asn Leu Glu Lys Ly - #s Ile Gln Gln Asn Trp                        1135     - #           1140      - #          1145                  - - CTT ACT CAT CAA ATT GTC TTC AAT CTT GGT TT - #T GAT GAC TTT ACT TCA          3678                                                                        Leu Thr His Gln Ile Val Phe Asn Leu Gly Ph - #e Asp Asp Phe Thr Ser                    1150         - #       1155          - #      1160                      - - GCG CTT CAG CAT AAA GAT TAT TTA ACT CGA CG - #T GTT ACC GCT ACG GCA          3726                                                                        Ala Leu Gln His Lys Asp Tyr Leu Thr Arg Ar - #g Val Thr Ala Thr Ala                1165             - #   1170              - #  1175                          - - AAG AGT ATT TCA GAG AAA GCT AAT GAA ACA AG - #A AGA AAT GGT TAC AAA          3774                                                                        Lys Ser Ile Ser Glu Lys Ala Asn Glu Thr Ar - #g Arg Asn Gly Tyr Lys            1180                1185 - #                1190 - #               1195         - - AAA CAA CCT TAC TTA TAC CCA AAA CCA ACA GT - #A GGT TTT GTA GTA CAA          3822                                                                        Lys Gln Pro Tyr Leu Tyr Pro Lys Pro Thr Va - #l Gly Phe Val Val Gln                            1200 - #               1205  - #              1210              - - GAT CAT TGT GAT TAT AAA GGT AAC TCC TCT AA - #T TAC AGA GAC TGT AAA          3870                                                                        Asp His Cys Asp Tyr Lys Gly Asn Ser Ser As - #n Tyr Arg Asp Cys Lys                        1215     - #           1220      - #          1225                  - - GTG CGG TTA ATT AAA GGG AAA AAT TAT TAT TT - #C GCA GCA CGC AAT AAT          3918                                                                        Val Arg Leu Ile Lys Gly Lys Asn Tyr Tyr Ph - #e Ala Ala Arg Asn Asn                    1230         - #       1235          - #      1240                      - - ATG GCA TTA GGG AAA TAC GTT GAT TTA GGT TT - #A GGT ATT CGG TAT GAC          3966                                                                        Met Ala Leu Gly Lys Tyr Val Asp Leu Gly Le - #u Gly Ile Arg Tyr Asp                1245             - #   1250              - #  1255                          - - GTA TCT CGC ACA AAA GCT AAT GAA TCA ACT AT - #T AGT GTT GGT AAA TTT          4014                                                                        Val Ser Arg Thr Lys Ala Asn Glu Ser Thr Il - #e Ser Val Gly Lys Phe            1260                1265 - #                1270 - #               1275         - - AAA AAT TTC TCT TGG AAT ACT GGT ATT GTC AT - #A AAA CCA ACG GAA TGG          4062                                                                        Lys Asn Phe Ser Trp Asn Thr Gly Ile Val Il - #e Lys Pro Thr Glu Trp                            1280 - #               1285  - #              1290              - - CTT GAT CTT TCT TAT CGC CTT TCT ACT GGA TT - #T AGA AAT CCT AGT TTT          4110                                                                        Leu Asp Leu Ser Tyr Arg Leu Ser Thr Gly Ph - #e Arg Asn Pro Ser Phe                        1295     - #           1300      - #          1305                  - - GCT GAA ATG TAT GGT TGG CGG TAT GGT GGC AA - #T AAT AGC GAG GTT TAT          4158                                                                        Ala Glu Met Tyr Gly Trp Arg Tyr Gly Gly As - #n Asn Ser Glu Val Tyr                    1310         - #       1315          - #      1320                      - - GTA GGT AAA TTT AAG CCT GAA ACA TCT CGT AA - #C CAA GAG TTT GGT CTC          4206                                                                        Val Gly Lys Phe Lys Pro Glu Thr Ser Arg As - #n Gln Glu Phe Gly Leu                1325             - #   1330              - #  1335                          - - GCT CTA AAA GGG GAT TTT GGT AAT ATT GAG AT - #C AGT CAT TTT AGT AAT          4254                                                                        Ala Leu Lys Gly Asp Phe Gly Asn Ile Glu Il - #e Ser His Phe Ser Asn            1340                1345 - #                1350 - #               1355         - - GCT TAT CGA AAT CTT ATC GCC TTT GCT GAA GA - #A CTT AAT AAA AAT GGA          4302                                                                        Ala Tyr Arg Asn Leu Ile Ala Phe Ala Glu Gl - #u Leu Asn Lys Asn Gly                            1360 - #               1365  - #              1370              - - ACT GGA AAG GCC AAT TAT GGA TAT CAT AAT GC - #A CAA AAT GCA AAA TTA          4350                                                                        Thr Gly Lys Ala Asn Tyr Gly Tyr His Asn Al - #a Gln Asn Ala Lys Leu                        1375     - #           1380      - #          1385                  - - GTT GGC GTA AAT ATA ACT GCG CAA TTA GAT TT - #T AAT GGT TTA TGG AAA          4398                                                                        Val Gly Val Asn Ile Thr Ala Gln Leu Asp Ph - #e Asn Gly Leu Trp Lys                    1390         - #       1395          - #      1400                      - - CGT ATT CCC TAC GGT TGG TAT GCA ACA TTT GC - #T TAT AAC CGA GTA AAA          4446                                                                        Arg Ile Pro Tyr Gly Trp Tyr Ala Thr Phe Al - #a Tyr Asn Arg Val Lys                1405             - #   1410              - #  1415                          - - GTT AAA GAT CAA AAA ATC AAT GCT GGT TTG GC - #C TCC GTA AGC AGT TAT          4494                                                                        Val Lys Asp Gln Lys Ile Asn Ala Gly Leu Al - #a Ser Val Ser Ser Tyr            1420                1425 - #                1430 - #               1435         - - TTA TTT GAT GCC ATT CAG CCC AGC CGT TAT AT - #C ATT GGT TTA GGC TAT          4542                                                                        Leu Phe Asp Ala Ile Gln Pro Ser Arg Tyr Il - #e Ile Gly Leu Gly Tyr                            1440 - #               1445  - #              1450              - - GAT CAT CCA AGT AAT ACT TGG GGA ATT AAT AC - #A ATG TTT ACT CAA TCA          4590                                                                        Asp His Pro Ser Asn Thr Trp Gly Ile Asn Th - #r Met Phe Thr Gln Ser                        1455     - #           1460      - #          1465                  - - AAA GCA AAA TCT CAA AAT GAA TTG CTA GGA AA - #A CGT GCA TTG GGT AAC          4638                                                                        Lys Ala Lys Ser Gln Asn Glu Leu Leu Gly Ly - #s Arg Ala Leu Gly Asn                    1470         - #       1475          - #      1480                      - - AAT TCA AGG GAT GTA AAA TCA ACA AGA AAA CT - #T ACT CGG GCA TGG CAT          4686                                                                        Asn Ser Arg Asp Val Lys Ser Thr Arg Lys Le - #u Thr Arg Ala Trp His                1485             - #   1490              - #  1495                          - - ATC TTA GAT GTA TCG GGT TAT TAC ATG GCG AA - #T AAA AAT ATT ATG CTT          4734                                                                        Ile Leu Asp Val Ser Gly Tyr Tyr Met Ala As - #n Lys Asn Ile Met Leu            1500                1505 - #                1510 - #               1515         - - CGA TTA GGG ATA TAT AAT TTA TTC AAC TAT CG - #C TAT GTT ACT TGG GAA          4782                                                                        Arg Leu Gly Ile Tyr Asn Leu Phe Asn Tyr Ar - #g Tyr Val Thr Trp Glu                            1520 - #               1525  - #              1530              - - GCG GTG CGT CAA ACA GCA CAA GGT GCG GTC AA - #T CAA CAT CAA AAT GTT          4830                                                                        Ala Val Arg Gln Thr Ala Gln Gly Ala Val As - #n Gln His Gln Asn Val                        1535     - #           1540      - #          1545                  - - GGT AGC TAT ACT CGC TAC GCA GCA TCA GGA CG - #A AAC TAT ACC TTA ACA          4878                                                                        Gly Ser Tyr Thr Arg Tyr Ala Ala Ser Gly Ar - #g Asn Tyr Thr Leu Thr                    1550         - #       1555          - #      1560                      - - TTA GAA ATG AAA TTCTAAATTA AAATGCGCCA GATGGACTAG AC - #ATGCTATA              4930                                                                        Leu Glu Met Lys                                                                    1565                                                                        - - TCTATACCTT ACTGGCGCAT CTTTTTCTGT TCTATAATCT GGTTAAGTGA AA -              #AACCAAAC   4990                                                                  - - TTGGATTTTT TAGAAGATCT TTCCACGCAT TTATTGTAAA ATCTCCGACA AT -             #TTTTACCG   5050                                                                  - - CACTTTTCTC TATTACAAAA ACAATAAGGA TCCTTTTGTG AATCTCTCA  - #                  5099                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:5:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 913 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:5:                                - - Met Thr Lys Lys Pro Tyr Phe Arg Leu Ser Il - #e Ile Ser Cys Leu Leu       1               5   - #                10  - #                15                - - Ile Ser Cys Tyr Val Lys Ala Glu Thr Gln Se - #r Ile Lys Asp Thr Lys                   20      - #            25      - #            30                    - - Glu Ala Ile Ser Ser Glu Val Asp Thr Gln Se - #r Thr Glu Asp Ser Glu               35          - #        40          - #        45                        - - Leu Glu Thr Ile Ser Val Thr Ala Glu Lys Va - #l Arg Asp Arg Lys Asp           50              - #    55              - #    60                            - - Asn Glu Val Thr Gly Leu Gly Lys Ile Ile Ly - #s Thr Ser Glu Ser Ile       65                  - #70                  - #75                  - #80         - - Ser Arg Glu Gln Val Leu Asn Ile Arg Asp Le - #u Thr Arg Tyr Asp Pro                       85  - #                90  - #                95                - - Gly Ile Ser Val Val Glu Gln Gly Arg Gly Al - #a Ser Ser Gly Tyr Ser                   100      - #           105      - #           110                   - - Ile Arg Gly Met Asp Arg Asn Arg Val Ala Le - #u Leu Val Asp Gly Leu               115          - #       120          - #       125                       - - Pro Gln Thr Gln Ser Tyr Val Val Gln Ser Pr - #o Leu Val Ala Arg Ser           130              - #   135              - #   140                           - - Gly Tyr Ser Gly Thr Gly Ala Ile Asn Glu Il - #e Glu Tyr Glu Asn Val       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Lys Ala Val Glu Ile Ser Lys Gly Gly Ser Se - #r Ser Glu Tyr Gly         Asn                                                                                              165  - #               170  - #               175              - - Gly Ala Leu Ala Gly Ser Val Thr Phe Gln Se - #r Lys Ser Ala Ala Asp                   180      - #           185      - #           190                   - - Ile Leu Glu Gly Asp Lys Ser Trp Gly Ile Gl - #n Thr Lys Asn Ala Tyr               195          - #       200          - #       205                       - - Ser Ser Lys Asn Lys Gly Phe Thr His Ser Le - #u Ala Val Ala Gly Lys           210              - #   215              - #   220                           - - Gln Gly Gly Phe Glu Gly Val Ala Ile Tyr Th - #r His Arg Asn Ser Ile       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Glu Thr Gln Val His Lys Asp Ala Leu Lys Gl - #y Val Gln Ser Tyr         Asp                                                                                              245  - #               250  - #               255              - - Arg Phe Ile Ala Thr Thr Glu Asp Gln Ser Al - #a Tyr Phe Val Met Gln                   260      - #           265      - #           270                   - - Asp Glu Cys Leu Asp Gly Tyr Asp Lys Cys Ly - #s Thr Ser Pro Lys Arg               275          - #       280          - #       285                       - - Pro Ala Thr Leu Ser Thr Gln Arg Glu Thr Va - #l Ser Val Ser Asp Tyr           290              - #   295              - #   300                           - - Thr Gly Ala Asn Arg Ile Lys Pro Asn Pro Me - #t Lys Tyr Glu Ser Gln       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Ser Trp Phe Leu Arg Gly Gly Tyr His Phe Se - #r Glu Gln His Tyr         Ile                                                                                              325  - #               330  - #               335              - - Gly Gly Ile Phe Glu Phe Thr Gln Gln Lys Ph - #e Asp Ile Arg Asp Met                   340      - #           345      - #           350                   - - Thr Phe Pro Ala Tyr Leu Arg Pro Thr Glu As - #p Lys Asp Leu Gln Ser               355          - #       360          - #       365                       - - Arg Pro Phe Tyr Pro Lys Gln Asp Tyr Gly Al - #a Tyr Gln His Ile Gly           370              - #   375              - #   380                           - - Asp Gly Arg Gly Val Lys Tyr Ala Ser Gly Le - #u Tyr Phe Asp Glu His       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - His Arg Lys Gln Arg Val Gly Ile Glu Tyr Il - #e Tyr Glu Asn Lys         Asn                                                                                              405  - #               410  - #               415              - - Lys Ala Gly Ile Ile Asp Lys Ala Val Leu Se - #r Ala Asn Gln Gln Asn                   420      - #           425      - #           430                   - - Ile Ile Leu Asp Ser Tyr Met Arg His Thr Hi - #s Cys Ser Leu Tyr Pro               435          - #       440          - #       445                       - - Asn Pro Ser Lys Asn Cys Arg Pro Thr Leu As - #p Lys Pro Tyr Ser Tyr           450              - #   455              - #   460                           - - Tyr His Ser Asp Arg Asn Val Tyr Lys Glu Ly - #s His Asn Met Leu Gln       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Leu Asn Leu Glu Lys Lys Ile Gln Gln Asn Tr - #p Leu Thr His Gln         Ile                                                                                              485  - #               490  - #               495              - - Ala Phe Asn Leu Gly Phe Asp Asp Phe Thr Se - #r Ala Leu Gln His Lys                   500      - #           505      - #           510                   - - Asp Tyr Leu Thr Arg Arg Val Ile Ala Thr Al - #a Ser Ser Ile Ser Glu               515          - #       520          - #       525                       - - Lys Arg Gly Glu Ala Arg Arg Asn Gly Leu Gl - #n Ser Ser Pro Tyr Leu           530              - #   535              - #   540                           - - Tyr Pro Thr Pro Lys Ala Glu Leu Val Gly Gl - #y Asp Leu Cys Asn Tyr       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Gln Gly Lys Ser Ser Asn Tyr Ser Asp Cys Ly - #s Val Arg Leu Ile         Lys                                                                                              565  - #               570  - #               575              - - Gly Lys Asn Tyr Tyr Phe Ala Ala Arg Asn As - #n Met Ala Leu Gly Lys                   580      - #           585      - #           590                   - - Tyr Val Asp Leu Gly Leu Gly Met Arg Tyr As - #p Val Ser Arg Thr Lys               595          - #       600          - #       605                       - - Ala Asn Glu Ser Thr Ile Ser Val Gly Lys Ph - #e Lys Asn Phe Ser Trp           610              - #   615              - #   620                           - - Asn Thr Gly Ile Val Ile Lys Pro Thr Glu Tr - #p Leu Asp Leu Ser Tyr       625                 6 - #30                 6 - #35                 6 -       #40                                                                               - - Arg Leu Ser Thr Gly Phe Arg Asn Pro Ser Ph - #e Ala Glu Met Tyr         Gly                                                                                              645  - #               650  - #               655              - - Trp Arg Tyr Gly Gly Lys Asp Thr Asp Val Ty - #r Ile Gly Lys Phe Lys                   660      - #           665      - #           670                   - - Pro Glu Thr Ser Arg Asn Gln Glu Phe Gly Le - #u Ala Leu Lys Gly Asp               675          - #       680          - #       685                       - - Phe Gly Asn Ile Glu Ile Ser His Phe Ser As - #n Ala Tyr Arg Asn Leu           690              - #   695              - #   700                           - - Ile Ala Phe Ala Glu Glu Leu Ser Lys Asn Gl - #y Thr Thr Gly Lys Gly       705                 7 - #10                 7 - #15                 7 -       #20                                                                               - - Asn Tyr Gly Tyr His Asn Ala Gln Asn Ala Ly - #s Leu Val Gly Val         Asn                                                                                              725  - #               730  - #               735              - - Ile Thr Ala Gln Leu Asp Phe Asn Gly Leu Tr - #p Lys Arg Ile Pro Tyr                   740      - #           745      - #           750                   - - Gly Trp Tyr Ala Thr Phe Ala Tyr Asn Arg Va - #l Lys Val Lys Asp Gln               755          - #       760          - #       765                       - - Lys Ile Asn Ala Gly Leu Ala Ser Val Ser Se - #r Tyr Leu Phe Asp Ala           770              - #   775              - #   780                           - - Ile Gln Pro Ser Arg Tyr Ile Ile Gly Leu Gl - #y Tyr Asp His Pro Ser       785                 7 - #90                 7 - #95                 8 -       #00                                                                               - - Asn Thr Trp Gly Ile Lys Thr Met Phe Thr Gl - #n Ser Lys Ala Lys         Ser                                                                                              805  - #               810  - #               815              - - Gln Asn Glu Leu Leu Gly Lys Arg Ala Leu Gl - #y Asn Asn Ser Arg Asn                   820      - #           825      - #           830                   - - Val Lys Ser Thr Arg Lys Leu Thr Arg Ala Tr - #p His Ile Leu Asp Val               835          - #       840          - #       845                       - - Ser Gly Tyr Tyr Met Val Asn Arg Ser Ile Le - #u Phe Arg Leu Gly Val           850              - #   855              - #   860                           - - Tyr Asn Leu Leu Asn Tyr Arg Tyr Val Thr Tr - #p Glu Ala Val Arg Gln       865                 8 - #70                 8 - #75                 8 -       #80                                                                               - - Thr Ala Gln Gly Ala Val Asn Gln His Gln As - #n Val Gly Asn Tyr         Thr                                                                                              885  - #               890  - #               895              - - Arg Tyr Ala Ala Ser Gly Arg Asn Tyr Thr Le - #u Thr Leu Glu Met Lys                   900      - #           905      - #           910                   - - Phe                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:6:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 644 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6:                                - - Met Lys Ser Val Pro Leu Ile Ser Gly Gly Le - #u Ser Phe Leu Leu Ser       1               5   - #                10  - #                15                - - Ala Cys Ser Gly Gly Gly Ser Phe Asp Val As - #p Asn Val Ser Asn Thr                   20      - #            25      - #            30                    - - Pro Ser Ser Lys Pro Arg Tyr Gln Asp Asp Th - #r Ser Ser Ser Arg Thr               35          - #        40          - #        45                        - - Lys Ser Lys Leu Glu Lys Leu Ser Ile Pro Se - #r Leu Gly Gly Gly Met           50              - #    55              - #    60                            - - Lys Leu Ala Ala Leu Asn Leu Phe Asp Arg As - #n Lys Pro Ser Leu Leu       65                  - #70                  - #75                  - #80         - - Asn Glu Asp Ser Tyr Met Ile Phe Ser Ser Ar - #g Ser Thr Ile Glu Glu                       85  - #                90  - #                95                - - Asp Val Lys Asn Asp Asn Gln Asn Gly Glu Hi - #s Pro Ile Asp Ser Ile                   100      - #           105      - #           110                   - - Val Asp Pro Arg Ala Pro Asn Ser Asn Glu As - #n Arg His Gly Gln Lys               115          - #       120          - #       125                       - - Tyr Val Tyr Ser Gly Leu Tyr Tyr Ile Gln Se - #r Trp Ser Leu Arg Asp           130              - #   135              - #   140                           - - Leu Pro Asn Lys Lys Phe Tyr Ser Gly Tyr Ty - #r Gly Tyr Ala Tyr Tyr       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Phe Gly Asn Thr Thr Ala Ser Ala Leu Pro Va - #l Gly Gly Val Ala         Thr                                                                                              165  - #               170  - #               175              - - Tyr Lys Gly Thr Trp Ser Phe Ile Thr Ala Al - #a Glu Asn Gly Lys Asn                   180      - #           185      - #           190                   - - Tyr Glu Leu Leu Arg Asn Ser Gly Gly Gly Gl - #n Ala Tyr Ser Arg Arg               195          - #       200          - #       205                       - - Ser Ala Thr Pro Glu Asp Ile Asp Leu Asp Ar - #g Lys Thr Gly Leu Thr           210              - #   215              - #   220                           - - Ser Glu Phe Thr Val Asn Phe Gly Thr Lys Ly - #s Leu Thr Gly Gly Leu       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Tyr Tyr Asn Leu Arg Glu Thr Asp Ala Asn Ly - #s Ser Gln Asn Arg         Thr                                                                                              245  - #               250  - #               255              - - His Lys Leu Tyr Asp Leu Glu Ala Asp Val Hi - #s Ser Asn Arg Phe Arg                   260      - #           265      - #           270                   - - Gly Lys Val Lys Pro Thr Lys Lys Glu Ser Se - #r Glu Glu His Pro Phe               275          - #       280          - #       285                       - - Thr Ser Glu Gly Thr Leu Glu Gly Gly Phe Ty - #r Gly Pro Glu Gly Gln           290              - #   295              - #   300                           - - Glu Leu Gly Gly Lys Phe Leu Ala His Asp Ly - #s Lys Val Leu Gly Val       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Phe Ser Ala Lys Glu Gln Gln Glu Thr Ser Gl - #u Asn Lys Lys Leu         Pro                                                                                              325  - #               330  - #               335              - - Lys Glu Thr Leu Ile Asp Gly Lys Leu Thr Th - #r Phe Lys Thr Thr Asn                   340      - #           345      - #           350                   - - Ala Thr Ala Asn Ala Thr Thr Asp Ala Thr Th - #r Ser Thr Thr Ala Ser               355          - #       360          - #       365                       - - Thr Lys Thr Asp Thr Thr Thr Asn Ala Thr Al - #a Asn Thr Glu Asn Phe           370              - #   375              - #   380                           - - Thr Thr Lys Asp Ile Pro Ser Leu Gly Glu Al - #a Asp Tyr Leu Leu Ile       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Asp Asn Tyr Pro Val Pro Leu Phe Pro Glu Se - #r Gly Asp Phe Ile         Ser                                                                                              405  - #               410  - #               415              - - Ser Lys His His Thr Val Gly Lys Lys Thr Ty - #r Gln Val Glu Ala Cys                   420      - #           425      - #           430                   - - Cys Ser Asn Leu Ser Tyr Val Lys Phe Gly Me - #t Tyr Tyr Glu Ala Pro               435          - #       440          - #       445                       - - Pro Lys Glu Glu Glu Lys Glu Lys Glu Lys As - #p Lys Asp Lys Glu Lys           450              - #   455              - #   460                           - - Glu Lys Gln Ala Thr Thr Ser Ile Lys Thr Ty - #r Tyr Gln Phe Leu Leu       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Gly Leu Arg Thr Pro Ser Ser Glu Ile Pro Ly - #s Glu Gly Ser Ala         Lys                                                                                              485  - #               490  - #               495              - - Tyr His Gly Asn Trp Phe Gly Tyr Ile Ser As - #p Gly Glu Thr Ser Tyr                   500      - #           505      - #           510                   - - Ser Ala Ser Gly Asp Lys Glu Arg Ser Lys As - #n Ala Val Ala Glu Phe               515          - #       520          - #       525                       - - Asn Val Asn Phe Ala Glu Lys Thr Leu Thr Gl - #y Glu Leu Lys Arg His           530              - #   535              - #   540                           - - Asp Thr Gln Asn Pro Val Phe Lys Ile Asn Al - #a Thr Phe Gln Ser Gly       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Lys Asn Asp Phe Thr Gly Thr Ala Thr Ala Ly - #s Asp Leu Ala Ile         Asp                                                                                              565  - #               570  - #               575              - - Gly Lys Asn Thr Gln Gly Thr Ser Lys Val As - #n Phe Thr Ala Thr Val                   580      - #           585      - #           590                   - - Asn Gly Ala Phe Tyr Gly Pro His Ala Thr Gl - #u Leu Gly Gly Tyr Phe               595          - #       600          - #       605                       - - Thr Tyr Asn Gly Asn Asn Pro Thr Asp Lys As - #n Ser Ser Ser Asn Ser           610              - #   615              - #   620                           - - Glu Lys Ala Arg Ala Ala Val Val Phe Gly Al - #a Lys Lys Gln Gln Val       625                 6 - #30                 6 - #35                 6 -       #40                                                                               - - Glu Thr Thr Lys                                                            - -  - - (2) INFORMATION FOR SEQ ID NO:7:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 912 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:7:                                - - Met Thr Lys Lys Pro Tyr Phe Arg Leu Ser Il - #e Ile Ser Cys Leu         Leu                                                                              1               5   - #                10  - #                15               - - Ile Ser Cys Tyr Val Lys Ala Glu Thr Gln Se - #r Ile Lys Asp Thr Lys                   20      - #            25      - #            30                    - - Glu Ala Ile Ser Ser Glu Val Asp Thr Gln Se - #r Thr Glu Asp Ser Glu               35          - #        40          - #        45                        - - Leu Glu Thr Ile Ser Val Thr Ala Glu Lys Il - #e Arg Asp Arg Lys Asp           50              - #    55              - #    60                            - - Asn Glu Val Thr Gly Leu Gly Lys Ile Ile Ly - #s Thr Ser Glu Ser Ile       65                  - #70                  - #75                  - #80         - - Ser Arg Glu Gln Val Leu Asn Ile Arg Asp Le - #u Thr Arg Tyr Asp Pro                       85  - #                90  - #                95                - - Gly Ile Ser Val Val Glu Gln Gly Arg Gly Al - #a Ser Ser Gly Tyr Ser                   100      - #           105      - #           110                   - - Ile Arg Gly Met Asp Arg Asn Arg Val Ala Le - #u Leu Val Asp Gly Leu               115          - #       120          - #       125                       - - Pro Gln Thr Gln Ser Tyr Val Val Gln Ser Pr - #o Leu Val Ala Arg Ser           130              - #   135              - #   140                           - - Gly Tyr Ser Gly Thr Gly Ala Ile Asn Glu Il - #e Glu Tyr Glu Asn Val       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Lys Ala Val Glu Ile Ser Lys Gly Gly Ser Se - #r Ser Glu Tyr Gly         Asn                                                                                              165  - #               170  - #               175              - - Gly Ala Leu Ala Gly Ser Val Thr Phe Gln Se - #r Lys Ser Ala Ala Asp                   180      - #           185      - #           190                   - - Ile Leu Glu Gly Asp Lys Ser Trp Gly Ile Gl - #n Thr Lys Asn Ala Tyr               195          - #       200          - #       205                       - - Ser Ser Lys Asn Lys Gly Phe Thr His Ser Le - #u Ala Val Ala Gly Lys           210              - #   215              - #   220                           - - Gln Gly Gly Phe Glu Gly Leu Ala Ile Tyr Th - #r Gln Arg Asn Ser Ile       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Glu Thr Gln Val His Lys Asp Ala Leu Lys Gl - #y Val Gln Ser Tyr         Asp                                                                                              245  - #               250  - #               255              - - Arg Leu Ile Ala Thr Thr Asp Lys Ser Ser Gl - #y Tyr Phe Val Ile Gln                   260      - #           265      - #           270                   - - Gly Glu Cys Pro Asn Gly Asp Asp Lys Cys Al - #a Ala Lys Pro Pro Ala               275          - #       280          - #       285                       - - Thr Leu Ser Thr Gln Ser Glu Thr Val Ser Va - #l Ser Asp Tyr Thr Gly           290              - #   295              - #   300                           - - Ala Asn Arg Ile Lys Pro Asn Pro Met Lys Ty - #r Glu Ser Gln Ser Trp       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Phe Leu Arg Gly Gly Tyr His Phe Ser Glu Gl - #n His Tyr Ile Gly         Gly                                                                                              325  - #               330  - #               335              - - Ile Phe Glu Phe Thr Gln Gln Lys Phe Asp Il - #e Arg Asp Met Thr Phe                   340      - #           345      - #           350                   - - Pro Ala Tyr Leu Ser Pro Thr Glu Arg Arg As - #p Asp Ser Ser Arg Ser               355          - #       360          - #       365                       - - Phe Tyr Pro Met Gln Asp His Gly Ala Tyr Gl - #n His Ile Glu Asp Gly           370              - #   375              - #   380                           - - Arg Gly Val Lys Tyr Ala Ser Gly Leu Tyr Ph - #e Asp Glu His His Arg       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Lys Gln Arg Val Gly Ile Glu Tyr Ile Tyr Gl - #u Asn Lys Asn Lys         Ala                                                                                              405  - #               410  - #               415              - - Gly Ile Ile Asp Lys Ala Val Leu Ser Ala As - #n Gln Gln Asn Ile Ile                   420      - #           425      - #           430                   - - Leu Asp Ser Tyr Met Arg His Thr His Cys Se - #r Leu Tyr Pro Asn Pro               435          - #       440          - #       445                       - - Ser Lys Asn Cys Arg Pro Thr Leu Asp Lys Pr - #o Tyr Ser Tyr Tyr Arg           450              - #   455              - #   460                           - - Ser Asp Arg Asn Val Tyr Lys Glu Lys His As - #n Met Leu Gln Leu Asn       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Leu Glu Lys Lys Ile Gln Gln Asn Trp Leu Th - #r His Gln Ile Val         Phe                                                                                              485  - #               490  - #               495              - - Asn Leu Gly Phe Asp Asp Phe Thr Ser Ala Le - #u Gln His Lys Asp Tyr                   500      - #           505      - #           510                   - - Leu Thr Arg Arg Val Ile Ala Thr Ala Asp Se - #r Ile Pro Arg Lys Pro               515          - #       520          - #       525                       - - Gly Glu Thr Gly Lys Pro Arg Asn Gly Leu Gl - #n Ser Gln Pro Tyr Leu           530              - #   535              - #   540                           - - Tyr Pro Lys Pro Glu Pro Tyr Phe Ala Gly Gl - #n Asp His Cys Asn Tyr       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Gln Gly Ser Ser Ser Asn Tyr Arg Asp Cys Ly - #s Val Arg Leu Ile         Lys                                                                                              565  - #               570  - #               575              - - Gly Lys Asn Tyr Tyr Phe Ala Ala Arg Asn As - #n Met Ala Leu Gly Lys                   580      - #           585      - #           590                   - - Tyr Val Asp Leu Gly Leu Gly Ile Arg Tyr As - #p Val Ser Arg Thr Lys               595          - #       600          - #       605                       - - Ala Asn Glu Ser Thr Ile Ser Val Gly Lys Ph - #e Lys Asn Phe Ser Trp           610              - #   615              - #   620                           - - Asn Thr Gly Ile Val Ile Lys Pro Thr Glu Tr - #p Leu Asp Leu Ser Tyr       625                 6 - #30                 6 - #35                 6 -       #40                                                                               - - Arg Leu Ser Thr Gly Phe Arg Asn Pro Ser Ph - #e Ser Glu Met Tyr         Gly                                                                                              645  - #               650  - #               655              - - Trp Arg Tyr Gly Gly Lys Asn Asp Glu Val Ty - #r Val Gly Lys Phe Lys                   660      - #           665      - #           670                   - - Pro Glu Thr Ser Arg Asn Gln Glu Phe Gly Le - #u Ala Leu Lys Gly Asp               675          - #       680          - #       685                       - - Phe Gly Asn Ile Glu Ile Ser His Phe Ser As - #n Ala Tyr Arg Asn Leu           690              - #   695              - #   700                           - - Ile Ala Phe Ala Glu Glu Leu Ser Lys Asn Gl - #y Thr Gly Lys Gly Asn       705                 7 - #10                 7 - #15                 7 -       #20                                                                               - - Tyr Gly Tyr His Asn Ala Gln Asn Ala Lys Le - #u Val Gly Val Asn         Ile                                                                                              725  - #               730  - #               735              - - Thr Ala Gln Leu Asp Phe Asn Gly Leu Trp Ly - #s Arg Ile Pro Tyr Gly                   740      - #           745      - #           750                   - - Trp Tyr Ala Thr Phe Ala Tyr Asn Gln Val Ly - #s Val Lys Asp Gln Lys               755          - #       760          - #       765                       - - Ile Asn Ala Gly Leu Ala Ser Val Ser Ser Ty - #r Leu Phe Asp Ala Ile           770              - #   775              - #   780                           - - Gln Pro Ser Arg Tyr Ile Ile Gly Leu Gly Ty - #r Asp His Pro Ser Asn       785                 7 - #90                 7 - #95                 8 -       #00                                                                               - - Thr Trp Gly Ile Asn Thr Met Phe Thr Gln Se - #r Lys Ala Lys Ser         Gln                                                                                              805  - #               810  - #               815              - - Asn Glu Leu Leu Gly Lys Arg Ala Leu Gly As - #n Asn Ser Arg Asp Val                   820      - #           825      - #           830                   - - Lys Ser Thr Arg Lys Leu Thr Arg Ala Trp Hi - #s Ile Leu Asp Val Ser               835          - #       840          - #       845                       - - Gly Tyr Tyr Met Ala Asn Lys Asn Ile Met Le - #u Arg Leu Gly Ile Tyr           850              - #   855              - #   860                           - - Asn Leu Phe Asn Tyr Arg Tyr Val Thr Trp Gl - #u Ala Val Arg Gln Thr       865                 8 - #70                 8 - #75                 8 -       #80                                                                               - - Ala Gln Gly Ala Val Asn Gln His Gln Asn Va - #l Gly Ser Tyr Thr         Arg                                                                                              885  - #               890  - #               895              - - Tyr Ala Ala Ser Gly Arg Asn Tyr Thr Leu Th - #r Leu Glu Met Lys Phe                   900      - #           905      - #           910                   - -  - - (2) INFORMATION FOR SEQ ID NO:8:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 660 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8:                                - - Met Lys Ser Val Pro Leu Ile Ser Gly Gly Le - #u Ser Phe Leu Leu Ser       1               5   - #                10  - #                15                - - Ala Cys Ser Gly Gly Gly Ser Phe Asp Val As - #p Asn Val Ser Asn Thr                   20      - #            25      - #            30                    - - Pro Ser Ser Lys Pro Arg Tyr Gln Asp Asp Th - #r Ser Asn Gln Arg Lys               35          - #        40          - #        45                        - - Lys Ser Asn Leu Lys Lys Leu Phe Ile Pro Se - #r Leu Gly Gly Gly Met           50              - #    55              - #    60                            - - Lys Leu Val Ala Gln Asn Leu Arg Gly Asn Ly - #s Glu Pro Ser Phe Leu       65                  - #70                  - #75                  - #80         - - Asn Glu Asp Asp Tyr Ile Ser Tyr Phe Ser Se - #r Leu Ser Thr Ile Glu                       85  - #                90  - #                95                - - Lys Asp Val Lys Asp Asn Asn Lys Asn Gly Al - #a Asp Leu Ile Gly Ser                   100      - #           105      - #           110                   - - Ile Asp Glu Pro Ser Thr Thr Asn Pro Pro Gl - #u Lys His His Gly Gln               115          - #       120          - #       125                       - - Lys Tyr Val Tyr Ser Gly Leu Tyr Tyr Thr Pr - #o Ser Trp Ser Leu Asn           130              - #   135              - #   140                           - - Asp Ser Lys Asn Lys Phe Tyr Leu Gly Tyr Ty - #r Gly Tyr Ala Phe Tyr       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Tyr Gly Asn Lys Thr Ala Thr Asn Leu Pro Va - #l Asn Gly Val Ala         Lys                                                                                              165  - #               170  - #               175              - - Tyr Lys Gly Thr Trp Asp Phe Ile Thr Ala Th - #r Lys Asn Gly Lys Arg                   180      - #           185      - #           190                   - - Tyr Pro Leu Leu Ser Asn Gly Ser His Ala Ty - #r Tyr Arg Arg Ser Ala               195          - #       200          - #       205                       - - Ile Pro Glu Asp Ile Asp Leu Glu Asn Asp Se - #r Lys Asn Gly Asp Ile           210              - #   215              - #   220                           - - Gly Leu Ile Ser Glu Phe Ser Ala Asp Phe Gl - #y Thr Lys Lys Leu Thr       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Gly Gln Leu Ser Tyr Thr Lys Arg Lys Thr As - #n Asn Gln Pro Tyr         Glu                                                                                              245  - #               250  - #               255              - - Lys Lys Lys Leu Tyr Asp Ile Asp Ala Asp Il - #e Tyr Ser Asn Arg Phe                   260      - #           265      - #           270                   - - Arg Gly Thr Val Lys Pro Thr Glu Lys Asp Se - #r Glu Glu His Pro Phe               275          - #       280          - #       285                       - - Thr Ser Glu Gly Thr Leu Glu Gly Gly Phe Ty - #r Gly Pro Asn Ala Glu           290              - #   295              - #   300                           - - Glu Leu Gly Gly Lys Phe Leu Ala Thr Asp As - #n Arg Val Phe Gly Val       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Phe Ser Ala Lys Glu Thr Glu Glu Thr Lys Ly - #s Glu Ala Leu Ser         Lys                                                                                              325  - #               330  - #               335              - - Glu Thr Leu Ile Asp Gly Lys Leu Ile Thr Ph - #e Ser Thr Lys Lys Thr                   340      - #           345      - #           350                   - - Asp Ala Lys Thr Asn Ala Thr Thr Ser Thr Al - #a Ala Asn Thr Thr Thr               355          - #       360          - #       365                       - - Asp Thr Thr Ala Asn Thr Ile Thr Asp Glu Ly - #s Asn Phe Lys Thr Glu           370              - #   375              - #   380                           - - Asp Ile Ser Ser Phe Gly Glu Ala Asp Tyr Le - #u Leu Ile Asp Lys Tyr       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Pro Ile Pro Leu Leu Pro Asp Lys Asn Thr As - #n Asp Phe Ile Ser         Ser                                                                                              405  - #               410  - #               415              - - Lys His His Thr Val Gly Asn Lys Arg Tyr Ly - #s Val Glu Ala Cys Cys                   420      - #           425      - #           430                   - - Ser Asn Leu Ser Tyr Val Lys Phe Gly Met Ty - #r Tyr Glu Asp Pro Leu               435          - #       440          - #       445                       - - Lys Glu Lys Glu Thr Glu Thr Glu Thr Glu Th - #r Glu Lys Asp Lys Glu           450              - #   455              - #   460                           - - Lys Glu Lys Glu Lys Asp Lys Asp Lys Glu Ly - #s Gln Thr Ala Ala Thr       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Thr Asn Thr Tyr Tyr Gln Phe Leu Leu Gly Hi - #s Arg Thr Pro Lys         Asp                                                                                              485  - #               490  - #               495              - - Asp Ile Pro Lys Thr Gly Ser Ala Lys Tyr Hi - #s Gly Ser Trp Phe Gly                   500      - #           505      - #           510                   - - Tyr Ile Thr Asp Gly Lys Thr Ser Tyr Ser Pr - #o Ser Gly Asp Lys Lys               515          - #       520          - #       525                       - - Arg Asp Lys Asn Ala Val Ala Glu Phe Asn Va - #l Asp Phe Ala Glu Lys           530              - #   535              - #   540                           - - Lys Leu Thr Gly Glu Leu Lys Arg His Asp Th - #r Gly Asn Pro Val Phe       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Ser Ile Glu Ala Asn Phe Asn Asn Ser Ser As - #n Ala Phe Thr Gly         Thr                                                                                              565  - #               570  - #               575              - - Ala Thr Ala Thr Asn Phe Val Ile Asp Gly Ly - #s Asn Ser Gln Asn Lys                   580      - #           585      - #           590                   - - Asn Thr Pro Ile Asn Ile Thr Thr Lys Val As - #n Gly Ala Phe Tyr Gly               595          - #       600          - #       605                       - - Pro Lys Ala Ser Glu Leu Gly Gly Tyr Phe Th - #r Tyr Asn Gly Asn Ser           610              - #   615              - #   620                           - - Thr Ala Thr Asn Ser Glu Ser Ser Ser Thr Va - #l Ser Ser Ser Ser Asn       625                 6 - #30                 6 - #35                 6 -       #40                                                                               - - Ser Lys Asn Ala Arg Ala Ala Val Val Phe Gl - #y Ala Arg Gln Gln         Val                                                                                              645  - #               650  - #               655              - - Glu Thr Thr Lys                                                                       660                                                                 - -  - - (2) INFORMATION FOR SEQ ID NO:9:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 912 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9:                                - - Met Thr Lys Lys Pro Tyr Phe Arg Leu Ser Il - #e Ile Ser Cys Leu Leu       1               5   - #                10  - #                15                - - Ile Ser Cys Tyr Val Lys Ala Glu Thr Gln Se - #r Ile Lys Asp Thr Lys                   20      - #            25      - #            30                    - - Glu Ala Ile Ser Ser Glu Val Asp Thr Gln Se - #r Thr Glu Asp Ser Glu               35          - #        40          - #        45                        - - Leu Glu Thr Ile Ser Val Thr Ala Glu Lys Il - #e Arg Asp Arg Lys Asp           50              - #    55              - #    60                            - - Asn Glu Val Thr Gly Leu Gly Lys Ile Ile Ly - #s Thr Ser Glu Ser Ile       65                  - #70                  - #75                  - #80         - - Ser Arg Glu Gln Val Leu Asn Ile Arg Asp Le - #u Thr Arg Tyr Asp Pro                       85  - #                90  - #                95                - - Gly Ile Ser Val Val Glu Gln Gly Arg Gly Al - #a Ser Ser Gly Tyr Ser                   100      - #           105      - #           110                   - - Ile Arg Gly Met Asp Arg Asn Arg Val Ala Le - #u Leu Val Asp Gly Leu               115          - #       120          - #       125                       - - Pro Gln Thr Gln Ser Tyr Val Val Gln Ser Pr - #o Leu Val Ala Arg Ser           130              - #   135              - #   140                           - - Gly Tyr Ser Gly Thr Gly Ala Ile Asn Glu Il - #e Glu Tyr Glu Asn Val       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Lys Ala Val Glu Ile Ser Lys Gly Gly Ser Se - #r Ser Glu Tyr Gly         Asn                                                                                              165  - #               170  - #               175              - - Gly Ala Leu Ala Gly Ser Val Thr Phe Gln Se - #r Lys Ser Ala Ala Asp                   180      - #           185      - #           190                   - - Ile Leu Glu Gly Asp Lys Ser Trp Gly Ile Gl - #n Thr Lys Asn Ala Tyr               195          - #       200          - #       205                       - - Ser Ser Lys Asn Lys Gly Phe Thr His Ser Le - #u Ala Val Ala Gly Lys           210              - #   215              - #   220                           - - Gln Gly Gly Phe Glu Gly Leu Ala Ile Tyr Th - #r Gln Arg Asn Ser Ile       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Glu Thr Gln Val His Lys Asp Ala Leu Lys Gl - #y Val Gln Ser Tyr         Asp                                                                                              245  - #               250  - #               255              - - Arg Leu Ile Ala Thr Thr Asp Lys Ser Ser Gl - #y Tyr Phe Val Ile Gln                   260      - #           265      - #           270                   - - Gly Glu Cys Pro Asn Gly Asp Asp Lys Cys Al - #a Ala Lys Pro Pro Ala               275          - #       280          - #       285                       - - Thr Leu Ser Thr Gln Ser Glu Thr Val Ser Va - #l Ser Asp Tyr Thr Gly           290              - #   295              - #   300                           - - Ala Asn Arg Ile Lys Pro Asn Pro Met Lys Ty - #r Glu Ser Gln Ser Trp       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Phe Leu Arg Gly Gly Tyr His Phe Ser Glu Gl - #n His Tyr Ile Gly         Gly                                                                                              325  - #               330  - #               335              - - Ile Phe Glu Phe Thr Gln Gln Lys Phe Asp Il - #e Arg Asp Met Thr Phe                   340      - #           345      - #           350                   - - Pro Ala Tyr Leu Ser Pro Thr Glu Arg Arg As - #p Asp Ser Ser Arg Ser               355          - #       360          - #       365                       - - Phe Tyr Pro Met Gln Asp His Gly Ala Tyr Gl - #n His Ile Glu Asp Gly           370              - #   375              - #   380                           - - Arg Gly Val Lys Tyr Ala Ser Gly Leu Tyr Ph - #e Asp Glu His His Arg       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Lys Gln Arg Val Gly Ile Glu Tyr Ile Tyr Gl - #u Asn Lys Asn Lys         Ala                                                                                              405  - #               410  - #               415              - - Gly Ile Ile Asp Lys Ala Val Leu Ser Ala As - #n Gln Gln Asn Ile Ile                   420      - #           425      - #           430                   - - Leu Asp Ser Tyr Met Arg His Thr His Cys Se - #r Leu Tyr Pro Asn Pro               435          - #       440          - #       445                       - - Ser Lys Asn Cys Arg Pro Thr Leu Asp Lys Pr - #o Tyr Ser Tyr Tyr Arg           450              - #   455              - #   460                           - - Ser Asp Arg Asn Val Tyr Lys Glu Lys His As - #n Met Leu Gln Leu Asn       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Leu Glu Lys Lys Ile Gln Gln Asn Trp Leu Th - #r His Gln Ile Val         Phe                                                                                              485  - #               490  - #               495              - - Asn Leu Gly Phe Asp Asp Phe Thr Ser Ala Le - #u Gln His Lys Asp Tyr                   500      - #           505      - #           510                   - - Leu Thr Arg Arg Val Ile Ala Thr Ala Asp Se - #r Ile Pro Arg Lys Pro               515          - #       520          - #       525                       - - Gly Glu Thr Gly Lys Pro Arg Asn Gly Leu Gl - #n Ser Gln Pro Tyr Leu           530              - #   535              - #   540                           - - Tyr Pro Lys Pro Glu Pro Tyr Phe Ala Gly Gl - #n Asp His Cys Asn Tyr       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Gln Gly Ser Ser Ser Asn Tyr Arg Asp Cys Ly - #s Val Arg Leu Ile         Lys                                                                                              565  - #               570  - #               575              - - Gly Lys Asn Tyr Tyr Phe Ala Ala Arg Asn As - #n Met Ala Leu Gly Lys                   580      - #           585      - #           590                   - - Tyr Val Asp Leu Gly Leu Gly Ile Arg Tyr As - #p Val Ser Arg Thr Lys               595          - #       600          - #       605                       - - Ala Asn Glu Ser Thr Ile Ser Val Gly Lys Ph - #e Lys Asn Phe Ser Trp           610              - #   615              - #   620                           - - Asn Thr Gly Ile Val Ile Lys Pro Thr Glu Tr - #p Leu Asp Leu Ser Tyr       625                 6 - #30                 6 - #35                 6 -       #40                                                                               - - Arg Leu Ser Thr Gly Phe Arg Asn Pro Ser Ph - #e Ser Glu Met Tyr         Gly                                                                                              645  - #               650  - #               655              - - Trp Arg Tyr Gly Gly Lys Asn Asp Glu Val Ty - #r Val Gly Lys Phe Lys                   660      - #           665      - #           670                   - - Pro Glu Thr Ser Arg Asn Gln Glu Phe Gly Le - #u Ala Leu Lys Gly Asp               675          - #       680          - #       685                       - - Phe Gly Asn Ile Glu Ile Ser His Phe Ser As - #n Ala Tyr Arg Asn Leu           690              - #   695              - #   700                           - - Ile Ala Phe Ala Glu Glu Leu Ser Lys Asn Gl - #y Thr Gly Lys Gly Asn       705                 7 - #10                 7 - #15                 7 -       #20                                                                               - - Tyr Gly Tyr His Asn Ala Gln Asn Ala Lys Le - #u Val Gly Val Asn         Ile                                                                                              725  - #               730  - #               735              - - Thr Ala Gln Leu Asp Phe Asn Gly Leu Trp Ly - #s Arg Ile Pro Tyr Gly                   740      - #           745      - #           750                   - - Trp Tyr Ala Thr Phe Ala Tyr Asn Gln Val Ly - #s Val Lys Asp Gln Lys               755          - #       760          - #       765                       - - Ile Asn Ala Gly Leu Ala Ser Val Ser Ser Ty - #r Leu Phe Asp Ala Ile           770              - #   775              - #   780                           - - Gln Pro Ser Arg Tyr Ile Ile Gly Leu Gly Ty - #r Asp His Pro Ser Asn       785                 7 - #90                 7 - #95                 8 -       #00                                                                               - - Thr Trp Gly Ile Asn Thr Met Phe Thr Gln Se - #r Lys Ala Lys Ser         Gln                                                                                              805  - #               810  - #               815              - - Asn Glu Leu Leu Gly Lys Arg Ala Leu Gly As - #n Asn Ser Arg Asp Val                   820      - #           825      - #           830                   - - Lys Ser Thr Arg Lys Leu Thr Arg Ala Trp Hi - #s Ile Leu Asp Val Ser               835          - #       840          - #       845                       - - Gly Tyr Tyr Met Ala Asn Lys Asn Ile Met Le - #u Arg Leu Gly Ile Tyr           850              - #   855              - #   860                           - - Asn Leu Phe Asn Tyr Arg Tyr Val Thr Trp Gl - #u Ala Val Arg Gln Thr       865                 8 - #70                 8 - #75                 8 -       #80                                                                               - - Ala Gln Gly Ala Val Asn Gln His Gln Asn Va - #l Gly Ser Tyr Thr         Arg                                                                                              885  - #               890  - #               895              - - Tyr Ala Ala Ser Gly Arg Asn Tyr Thr Leu Th - #r Leu Glu Met Lys Phe                   900      - #           905      - #           910                   - -  - - (2) INFORMATION FOR SEQ ID NO:10:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 660 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:10:                               - - Met Lys Ser Val Pro Leu Ile Ser Gly Gly Le - #u Ser Phe Leu Leu Ser       1               5   - #                10  - #                15                - - Ala Cys Ser Gly Gly Gly Ser Phe Asp Val As - #p Asn Val Ser Asn Thr                   20      - #            25      - #            30                    - - Pro Ser Ser Lys Pro Arg Tyr Gln Asp Asp Th - #r Ser Asn Gln Arg Lys               35          - #        40          - #        45                        - - Lys Ser Asn Leu Lys Lys Leu Phe Ile Pro Se - #r Leu Gly Gly Gly Met           50              - #    55              - #    60                            - - Lys Leu Val Ala Gln Asn Leu Arg Gly Asn Ly - #s Glu Pro Ser Phe Leu       65                  - #70                  - #75                  - #80         - - Asn Glu Asp Asp Tyr Ile Ser Tyr Phe Ser Se - #r Leu Ser Thr Ile Glu                       85  - #                90  - #                95                - - Lys Asp Val Lys Asp Asn Asn Lys Asn Gly Al - #a Asp Leu Ile Gly Ser                   100      - #           105      - #           110                   - - Ile Asp Glu Pro Ser Thr Thr Asn Pro Pro Gl - #u Lys His His Gly Gln               115          - #       120          - #       125                       - - Lys Tyr Val Tyr Ser Gly Leu Tyr Tyr Thr Pr - #o Ser Trp Ser Leu Asn           130              - #   135              - #   140                           - - Asp Ser Lys Asn Lys Phe Tyr Leu Gly Tyr Ty - #r Gly Tyr Ala Phe Tyr       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Tyr Gly Asn Lys Thr Ala Thr Asn Leu Pro Va - #l Asn Gly Val Ala         Lys                                                                                              165  - #               170  - #               175              - - Tyr Lys Gly Thr Trp Asp Phe Ile Thr Ala Th - #r Lys Asn Gly Lys Arg                   180      - #           185      - #           190                   - - Tyr Pro Leu Leu Ser Asn Gly Ser His Ala Ty - #r Tyr Arg Arg Ser Ala               195          - #       200          - #       205                       - - Ile Pro Glu Asp Ile Asp Leu Glu Asn Asp Se - #r Lys Asn Gly Asp Ile           210              - #   215              - #   220                           - - Gly Leu Ile Ser Glu Phe Ser Ala Asp Phe Gl - #y Thr Lys Lys Leu Thr       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Gly Gln Leu Ser Tyr Thr Lys Arg Lys Thr As - #n Asn Gln Pro Tyr         Glu                                                                                              245  - #               250  - #               255              - - Lys Lys Lys Leu Tyr Asp Ile Asp Ala Asp Il - #e Tyr Ser Asn Arg Phe                   260      - #           265      - #           270                   - - Arg Gly Thr Val Lys Pro Thr Glu Lys Asp Se - #r Glu Glu His Pro Phe               275          - #       280          - #       285                       - - Thr Ser Glu Gly Thr Leu Glu Gly Gly Phe Ty - #r Gly Pro Asn Ala Glu           290              - #   295              - #   300                           - - Glu Leu Gly Gly Lys Phe Leu Ala Thr Asp As - #n Arg Val Phe Gly Val       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Phe Ser Ala Lys Glu Thr Glu Glu Thr Lys Ly - #s Glu Ala Leu Ser         Lys                                                                                              325  - #               330  - #               335              - - Glu Thr Leu Ile Asp Gly Lys Leu Ile Thr Ph - #e Ser Thr Lys Lys Thr                   340      - #           345      - #           350                   - - Asp Ala Lys Thr Asn Ala Thr Thr Ser Thr Al - #a Ala Asn Thr Thr Thr               355          - #       360          - #       365                       - - Asp Thr Thr Ala Asn Thr Ile Thr Asp Glu Ly - #s Asn Phe Lys Thr Glu           370              - #   375              - #   380                           - - Asp Ile Ser Ser Phe Gly Glu Ala Asp Tyr Le - #u Leu Ile Asp Lys Tyr       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Pro Ile Pro Leu Leu Pro Asp Lys Asn Thr As - #n Asp Phe Ile Ser         Ser                                                                                              405  - #               410  - #               415              - - Lys His His Thr Val Gly Asn Lys Arg Tyr Ly - #s Val Glu Ala Cys Cys                   420      - #           425      - #           430                   - - Ser Asn Leu Ser Tyr Val Lys Phe Gly Met Ty - #r Tyr Glu Asp Pro Leu               435          - #       440          - #       445                       - - Lys Glu Lys Glu Thr Glu Thr Glu Thr Glu Th - #r Glu Lys Asp Lys Glu           450              - #   455              - #   460                           - - Lys Glu Lys Glu Lys Asp Lys Asp Lys Glu Ly - #s Gln Thr Ala Ala Thr       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Thr Asn Thr Tyr Tyr Gln Phe Leu Leu Gly Hi - #s Arg Thr Pro Lys         Asp                                                                                              485  - #               490  - #               495              - - Asp Ile Pro Lys Thr Gly Ser Ala Lys Tyr Hi - #s Gly Ser Trp Phe Gly                   500      - #           505      - #           510                   - - Tyr Ile Thr Asp Gly Lys Thr Ser Tyr Ser Pr - #o Ser Gly Asp Lys Lys               515          - #       520          - #       525                       - - Arg Asp Lys Asn Ala Val Ala Glu Phe Asn Va - #l Asp Phe Ala Glu Lys           530              - #   535              - #   540                           - - Lys Leu Thr Gly Glu Leu Lys Arg His Asp Th - #r Gly Asn Pro Val Phe       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Ser Ile Glu Ala Asn Phe Asn Asn Ser Ser As - #n Ala Phe Thr Gly         Thr                                                                                              565  - #               570  - #               575              - - Ala Thr Ala Thr Asn Phe Val Ile Asp Gly Ly - #s Asn Ser Gln Asn Lys                   580      - #           585      - #           590                   - - Asn Thr Pro Ile Asn Ile Thr Thr Lys Val As - #n Gly Ala Phe Tyr Gly               595          - #       600          - #       605                       - - Pro Lys Ala Ser Glu Leu Gly Gly Tyr Phe Th - #r Tyr Asn Gly Asn Ser           610              - #   615              - #   620                           - - Thr Ala Thr Asn Ser Glu Ser Ser Ser Thr Va - #l Ser Ser Ser Ser Asn       625                 6 - #30                 6 - #35                 6 -       #40                                                                               - - Ser Lys Asn Ala Arg Ala Ala Val Val Phe Gl - #y Ala Arg Gln Gln         Val                                                                                              645  - #               650  - #               655              - - Glu Thr Thr Lys                                                                       660                                                                 - -  - - (2) INFORMATION FOR SEQ ID NO:11:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 914 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:11:                               - - Met Thr Lys Lys Pro Tyr Phe Arg Leu Ser Il - #e Ile Ser Cys Leu Leu       1               5   - #                10  - #                15                - - Ile Ser Cys Tyr Val Lys Ala Glu Thr Gln Se - #r Ile Lys Asp Thr Lys                   20      - #            25      - #            30                    - - Glu Ala Ile Ser Ser Glu Val Asp Thr Gln Se - #r Thr Glu Asp Ser Glu               35          - #        40          - #        45                        - - Leu Glu Thr Ile Ser Val Thr Ala Glu Lys Il - #e Arg Asp Arg Lys Asp           50              - #    55              - #    60                            - - Asn Glu Val Thr Gly Leu Gly Lys Ile Ile Ly - #s Thr Ser Glu Ser Ile       65                  - #70                  - #75                  - #80         - - Ser Arg Glu Gln Val Leu Asn Ile Arg Asp Le - #u Thr Arg Tyr Asp Pro                       85  - #                90  - #                95                - - Gly Ile Ser Val Val Glu Gln Gly Arg Gly Al - #a Ser Ser Gly Tyr Ser                   100      - #           105      - #           110                   - - Ile Arg Gly Met Asp Arg Asn Arg Val Ala Le - #u Leu Val Asp Gly Leu               115          - #       120          - #       125                       - - Pro Gln Thr Gln Ser Tyr Val Val Gln Ser Pr - #o Leu Val Ala Arg Ser           130              - #   135              - #   140                           - - Gly Tyr Ser Gly Thr Gly Ala Ile Asn Glu Il - #e Glu Tyr Glu Asn Val       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Lys Ala Val Glu Ile Ser Lys Gly Gly Ser Se - #r Ser Glu Tyr Gly         Asn                                                                                              165  - #               170  - #               175              - - Gly Ala Leu Ala Gly Ser Val Thr Phe Gln Se - #r Lys Ser Ala Ala Asp                   180      - #           185      - #           190                   - - Ile Leu Glu Gly Asp Lys Ser Trp Gly Ile Gl - #n Thr Lys Asn Ala Tyr               195          - #       200          - #       205                       - - Ser Ser Lys Asn Lys Gly Phe Thr His Ser Le - #u Ala Val Ala Gly Lys           210              - #   215              - #   220                           - - Gln Gly Gly Phe Asp Gly Val Ala Ile Tyr Th - #r Gln Arg Asn Ser Ile       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Glu Thr Gln Val His Lys Asp Ala Leu Lys Gl - #y Val Gln Ser Tyr         His                                                                                              245  - #               250  - #               255              - - Arg Leu Ile Ala Lys Pro Glu Asp Gln Ser Al - #a Tyr Phe Val Met Gln                   260      - #           265      - #           270                   - - Asp Glu Cys Pro Lys Pro Asp Asp Tyr Asn Se - #r Cys Leu Pro Phe Ala               275          - #       280          - #       285                       - - Lys Arg Pro Ala Ile Leu Ser Ser Gln Arg Gl - #u Thr Val Ser Val Ser           290              - #   295              - #   300                           - - Asp Tyr Thr Gly Ala Asn Arg Ile Lys Pro As - #n Pro Met Lys Tyr Glu       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Ser Gln Ser Trp Phe Leu Arg Gly Gly Tyr Hi - #s Phe Ser Glu Gln         His                                                                                              325  - #               330  - #               335              - - Tyr Ile Gly Gly Ile Phe Glu Phe Thr Gln Gl - #n Lys Phe Asp Ile Arg                   340      - #           345      - #           350                   - - Asp Met Thr Phe Pro Ala Tyr Leu Arg Ser Th - #r Glu Lys Arg Asp Asp               355          - #       360          - #       365                       - - Ser Ser Gly Ser Phe Tyr Pro Lys Gln Asp Ty - #r Gly Ala Tyr Gln Arg           370              - #   375              - #   380                           - - Ile Glu Asp Gly Arg Gly Val Asn Tyr Ala Se - #r Gly Leu Tyr Phe Asp       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Glu His His Arg Lys Gln Arg Val Gly Ile Gl - #u Tyr Ile Tyr Glu         Asn                                                                                              405  - #               410  - #               415              - - Lys Asn Lys Ala Gly Ile Ile Asp Lys Ala Va - #l Leu Ser Ala Asn Gln                   420      - #           425      - #           430                   - - Gln Asn Ile Ile Leu Asp Ser Tyr Met Gln Hi - #s Thr His Cys Ser Leu               435          - #       440          - #       445                       - - Tyr Pro Asn Pro Ser Lys Asn Cys Arg Pro Th - #r Arg Asp Lys Pro Tyr           450              - #   455              - #   460                           - - Ser Tyr Tyr His Ser Asp Arg Asn Val Tyr Ly - #s Glu Lys His Asn Met       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Leu Gln Leu Asn Leu Glu Lys Lys Ile Gln Gl - #n Asn Trp Leu Thr         His                                                                                              485  - #               490  - #               495              - - Gln Ile Val Phe Asn Leu Gly Phe Asp Asp Ph - #e Thr Ser Ala Leu Gln                   500      - #           505      - #           510                   - - His Lys Asp Tyr Leu Thr Arg Arg Val Thr Al - #a Thr Ala Lys Ser Ile               515          - #       520          - #       525                       - - Ser Glu Lys Ala Asn Glu Thr Arg Arg Asn Gl - #y Tyr Lys Lys Gln Pro           530              - #   535              - #   540                           - - Tyr Leu Tyr Pro Lys Pro Thr Val Gly Phe Va - #l Val Gln Asp His Cys       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Asp Tyr Lys Gly Asn Ser Ser Asn Tyr Arg As - #p Cys Lys Val Arg         Leu                                                                                              565  - #               570  - #               575              - - Ile Lys Gly Lys Asn Tyr Tyr Phe Ala Ala Ar - #g Asn Asn Met Ala Leu                   580      - #           585      - #           590                   - - Gly Lys Tyr Val Asp Leu Gly Leu Gly Ile Ar - #g Tyr Asp Val Ser Arg               595          - #       600          - #       605                       - - Thr Lys Ala Asn Glu Ser Thr Ile Ser Val Gl - #y Lys Phe Lys Asn Phe           610              - #   615              - #   620                           - - Ser Trp Asn Thr Gly Ile Val Ile Lys Pro Th - #r Glu Trp Leu Asp Leu       625                 6 - #30                 6 - #35                 6 -       #40                                                                               - - Ser Tyr Arg Leu Ser Thr Gly Phe Arg Asn Pr - #o Ser Phe Ala Glu         Met                                                                                              645  - #               650  - #               655              - - Tyr Gly Trp Arg Tyr Gly Gly Asn Asn Ser Gl - #u Val Tyr Val Gly Lys                   660      - #           665      - #           670                   - - Phe Lys Pro Glu Thr Ser Arg Asn Gln Glu Ph - #e Gly Leu Ala Leu Lys               675          - #       680          - #       685                       - - Gly Asp Phe Gly Asn Ile Glu Ile Ser His Ph - #e Ser Asn Ala Tyr Arg           690              - #   695              - #   700                           - - Asn Leu Ile Ala Phe Ala Glu Glu Leu Asn Ly - #s Asn Gly Thr Gly Lys       705                 7 - #10                 7 - #15                 7 -       #20                                                                               - - Ala Asn Tyr Gly Tyr His Asn Ala Gln Asn Al - #a Lys Leu Val Gly         Val                                                                                              725  - #               730  - #               735              - - Asn Ile Thr Ala Gln Leu Asp Phe Asn Gly Le - #u Trp Lys Arg Ile Pro                   740      - #           745      - #           750                   - - Tyr Gly Trp Tyr Ala Thr Phe Ala Tyr Asn Ar - #g Val Lys Val Lys Asp               755          - #       760          - #       765                       - - Gln Lys Ile Asn Ala Gly Leu Ala Ser Val Se - #r Ser Tyr Leu Phe Asp           770              - #   775              - #   780                           - - Ala Ile Gln Pro Ser Arg Tyr Ile Ile Gly Le - #u Gly Tyr Asp His Pro       785                 7 - #90                 7 - #95                 8 -       #00                                                                               - - Ser Asn Thr Trp Gly Ile Asn Thr Met Phe Th - #r Gln Ser Lys Ala         Lys                                                                                              805  - #               810  - #               815              - - Ser Gln Asn Glu Leu Leu Gly Lys Arg Ala Le - #u Gly Asn Asn Ser Arg                   820      - #           825      - #           830                   - - Asp Val Lys Ser Thr Arg Lys Leu Thr Arg Al - #a Trp His Ile Leu Asp               835          - #       840          - #       845                       - - Val Ser Gly Tyr Tyr Met Ala Asn Lys Asn Il - #e Met Leu Arg Leu Gly           850              - #   855              - #   860                           - - Ile Tyr Asn Leu Phe Asn Tyr Arg Tyr Val Th - #r Trp Glu Ala Val Arg       865                 8 - #70                 8 - #75                 8 -       #80                                                                               - - Gln Thr Ala Gln Gly Ala Val Asn Gln His Gl - #n Asn Val Gly Ser         Tyr                                                                                              885  - #               890  - #               895              - - Thr Arg Tyr Ala Ala Ser Gly Arg Asn Tyr Th - #r Leu Thr Leu Glu Met                   900      - #           905      - #           910                   - - Lys Phe                                                                    - -  - - (2) INFORMATION FOR SEQ ID NO:12:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 654 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12:                               - - Met Lys Ser Val Pro Leu Ile Thr Gly Gly Le - #u Ser Phe Leu Leu Ser       1               5   - #                10  - #                15                - - Ala Cys Ser Gly Gly Gly Gly Ser Phe Asp Va - #l Asp Asp Val Ser Asn                   20      - #            25      - #            30                    - - Pro Ser Ser Ser Lys Pro Arg Tyr Gln Asp As - #p Thr Ser Asn Gln Arg               35          - #        40          - #        45                        - - Thr Lys Ser Asp Leu Glu Lys Leu Phe Ile Pr - #o Ser Leu Gly Gly Gly           50              - #    55              - #    60                            - - Met Lys Leu Val Ala Gln Asn Phe Ile Gly Al - #a Arg Glu Pro Ser Phe       65                  - #70                  - #75                  - #80         - - Leu Asn Glu Asp Gly Tyr Met Ile Phe Ser Se - #r Leu Ser Thr Ile Glu                       85  - #                90  - #                95                - - Glu Asp Val Glu Lys Val Lys Asn Asn Asn Ly - #s Asn Gly Gly Arg Leu                   100      - #           105      - #           110                   - - Ile Gly Ser Ile Glu Glu Pro Asn Gly Thr Se - #r Gln Asn Ser Asn Ser               115          - #       120          - #       125                       - - Gln Glu Tyr Val Tyr Ser Gly Leu Tyr Tyr Il - #e Asp Ser Trp Arg Asp           130              - #   135              - #   140                           - - Tyr Lys Lys Glu Glu Gln Lys Ala Tyr Thr Gl - #y Tyr Tyr Gly Tyr Ala       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Phe Tyr Tyr Gly Asn Glu Thr Ala Lys Asn Le - #u Pro Val Lys Gly         Val                                                                                              165  - #               170  - #               175              - - Ala Lys Tyr Lys Gly Thr Trp Asn Phe Ile Th - #r Ala Thr Glu Asn Gly                   180      - #           185      - #           190                   - - Lys Arg Tyr Ser Leu Phe Ser Asn Ser Ile Gl - #y Gln Ala Tyr Ser Arg               195          - #       200          - #       205                       - - Arg Ser Ala Ile Ser Glu Asp Ile Tyr Asn Le - #u Glu Asn Gly Asp Ala           210              - #   215              - #   220                           - - Gly Leu Ile Ser Glu Phe Ser Val Asp Phe Gl - #y Lys Lys Glu Leu Thr       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Gly Glu Leu Tyr Tyr Asn Glu Arg Lys Thr Se - #r Val Asn Glu Ser         Gln                                                                                              245  - #               250  - #               255              - - Asn Thr Thr His Lys Leu Tyr Thr Leu Glu Al - #a Lys Val Tyr Ser Asn                   260      - #           265      - #           270                   - - Arg Phe Arg Gly Lys Val Lys Pro Thr Lys Th - #r Lys Ser Glu Asp His               275          - #       280          - #       285                       - - Pro Phe Thr Ser Glu Gly Thr Leu Glu Gly Gl - #y Phe Tyr Gly Pro Asn           290              - #   295              - #   300                           - - Ala Glu Glu Leu Gly Gly Lys Phe Leu Ala As - #n Asp Glu Lys Val Phe       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Gly Val Phe Ser Ala Lys Glu Asp Pro Gln As - #n Pro Glu Asn Gln         Lys                                                                                              325  - #               330  - #               335              - - Leu Ser Thr Glu Thr Leu Ile Asp Gly Lys Le - #u Ile Thr Phe Lys Arg                   340      - #           345      - #           350                   - - Thr Asp Ala Thr Thr Asn Ala Thr Thr Asp Al - #a Lys Thr Ser Ala Thr               355          - #       360          - #       365                       - - Thr Asp Ala Thr Ser Thr Thr Ala Asn Lys Ly - #s Thr Asp Ala Glu Asn           370              - #   375              - #   380                           - - Phe Lys Thr Glu Asp Ile Pro Ser Phe Gly Gl - #u Ala Asp Tyr Leu Leu       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Ile Gly Asn Gln Pro Ile Pro Leu Leu Pro Gl - #u Lys Asn Thr Asp         Asp                                                                                              405  - #               410  - #               415              - - Phe Ile Ser Ser Lys His His Thr Val Gly Gl - #y Lys Thr Tyr Lys Val                   420      - #           425      - #           430                   - - Glu Ala Cys Cys Lys Asn Leu Ser Tyr Val Ly - #s Phe Gly Met Tyr Tyr               435          - #       440          - #       445                       - - Glu Asp Lys Asp Lys Asp Asn Lys Asn Glu Th - #r Asp Lys Glu Lys Gly           450              - #   455              - #   460                           - - Lys Glu Lys Pro Thr Thr Thr Thr Ser Ile As - #n Thr Tyr Tyr Gln Phe       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Leu Leu Gly Leu Arg Thr Pro Lys Asp Glu Il - #e Pro Lys Glu Gly         Ser                                                                                              485  - #               490  - #               495              - - Ala Lys Tyr His Gly Asn Trp Phe Gly Tyr Il - #e Ser Asp Gly Glu Thr                   500      - #           505      - #           510                   - - Ser Tyr Ser Ala Ser Gly Asp Lys Glu Arg Se - #r Lys Asn Ala Val Ala               515          - #       520          - #       525                       - - Glu Phe Asp Val Ser Phe Ala Asn Lys Thr Le - #u Thr Gly Glu Leu Lys           530              - #   535              - #   540                           - - Arg His Asp Asn Gly Asn Thr Val Phe Lys Il - #e Asn Ala Glu Leu Asn       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Gly Ser Asn Asp Phe Thr Gly Thr Ala Thr Al - #a Thr Asn Phe Val         Ile                                                                                              565  - #               570  - #               575              - - Asp Gly Asn Asn Ser Gln Thr Ser Asn Ala Ly - #s Ile Asn Ile Thr Thr                   580      - #           585      - #           590                   - - Lys Val Asn Gly Ala Phe Tyr Gly Pro Lys Al - #a Ser Glu Leu Gly Gly               595          - #       600          - #       605                       - - Tyr Phe Thr Tyr Asn Gly Lys Asn Pro Thr Al - #a Thr Asn Ser Glu Ser           610              - #   615              - #   620                           - - Ser Ser Thr Val Pro Ser Pro Pro Asn Ser Pr - #o Asn Ala Ser Ala Ala       625                 6 - #30                 6 - #35                 6 -       #40                                                                               - - Val Val Phe Gly Ala Lys Lys Gln Val Glu Th - #r Thr Asn Lys                              645  - #               650                                      - -  - - (2) INFORMATION FOR SEQ ID NO:13:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 36 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:13:                               - - Ala Glu Thr Gln Ser Ile Lys Asp Thr Lys Gl - #u Ala Ile Ser Ser Glu       1               5   - #                10  - #                15                - - Val Asp Thr Gln Ser Thr Glu Asp Ser Glu Le - #u Glu Thr Ile Ser Val                   20      - #            25      - #            30                    - - Thr Ala Glu Lys                                                                   35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:14:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 36 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:14:                               - - Ser Val Thr Ala Glu Lys Val Arg Asp Arg Ly - #s Asp Asn Glu Val Thr       1               5   - #                10  - #                15                - - Gly Leu Gly Lys Ile Ile Lys Thr Ser Glu Se - #r Ile Ser Arg Glu Gln                   20      - #            25      - #            30                    - - Val Leu Asn Ile                                                                   35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:15:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 36 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:15:                               - - Ser Arg Glu Gln Val Leu Asn Ile Arg Asp Le - #u Thr Arg Tyr Asp Pro       1               5   - #                10  - #                15                - - Gly Ile Ser Val Val Glu Gln Gly Arg Gly Al - #a Ser Ser Gly Tyr Ser                   20      - #            25      - #            30                    - - Ile Arg Gly Met                                                                   35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:16:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 36 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:16:                               - - Gly Tyr Ser Ile Arg Gly Met Asp Arg Asn Ar - #g Val Ala Leu Leu Val       1               5   - #                10  - #                15                - - Asp Gly Leu Pro Gln Thr Gln Ser Tyr Val Va - #l Gln Ser Pro Leu Val                   20      - #            25      - #            30                    - - Ala Arg Ser Gly                                                                   35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:17:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 36 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:17:                               - - Pro Leu Val Ala Arg Ser Gly Tyr Gly Thr Gl - #y Ala Ile Asn Glu Ile       1               5   - #                10  - #                15                - - Glu Tyr Glu Asn Val Lys Ala Val Glu Ile Se - #r Lys Gly Gly Ser Ser                   20      - #            25      - #            30                    - - Ser Glu Tyr Gly                                                                   35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:18:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 36 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:18:                               - - Ser Ser Ser Glu Tyr Gly Asn Gly Ala Leu Al - #a Gly Ser Val Thr Phe       1               5   - #                10  - #                15                - - Gln Ser Lys Ser Ala Ala Asp Ile Leu Glu Gl - #y Asp Lys Ser Trp Gly                   20      - #            25      - #            30                    - - Ile Gln Thr Lys                                                                   35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:19:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 36 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:19:                               - - Gly Ile Gln Thr Lys Asn Ala Tyr Ser Ser Ly - #s Asn Lys Gly Phe Thr       1               5   - #                10  - #                15                - - His Ser Leu Ala Val Ala Gly Lys Gln Gly Gl - #y Phe Glu Gly Val Ala                   20      - #            25      - #            30                    - - Ile Tyr Thr His                                                                   35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:20:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 36 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:20:                               - - Gly Val Ala Ile Tyr Thr His Arg Asn Ser Il - #e Glu Thr Gln Val His       1               5   - #                10  - #                15                - - Lys Asp Ala Leu Lys Gly Val Gln Ser Tyr As - #p Arg Phe Ile Ala Thr                   20      - #            25      - #            30                    - - Thr Glu Asp Gln                                                                   35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:21:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 36 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:21:                               - - Ile Ala Thr Thr Glu Asp Gln Ser Ala Tyr Ph - #e Val Met Gln Asp Glu       1               5   - #                10  - #                15                - - Cys Leu Asp Gly Tyr Asp Lys Cys Lys Thr Se - #r Pro Lys Arg Pro Ala                   20      - #            25      - #            30                    - - Thr Leu Ser Thr                                                                   35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:22:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 36 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:22:                               - - Pro Ala Thr Leu Ser Thr Gln Arg Glu Thr Va - #l Ser Val Ser Asp Tyr       1               5   - #                10  - #                15                - - Thr Gly Ala Asn Arg Ile Lys Pro Asn Pro Me - #t Lys Tyr Glu Ser Gln                   20      - #            25      - #            30                    - - Ser Trp Phe Leu                                                                   35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:23:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 36 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:23:                               - - Tyr Glu Ser Gln Ser Trp Phe Leu Arg Gly Gl - #y Tyr His Phe Ser Glu       1               5   - #                10  - #                15                - - Gln His Tyr Ile Gly Gly Ile Phe Glu Phe Th - #r Gln Gln Lys Phe Asp                   20      - #            25      - #            30                    - - Ile Arg Asp Met                                                                   35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:24:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 36 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:24:                               - - Lys Phe Asp Ile Arg Asp Met Thr Phe Pro Al - #a Tyr Leu Arg Pro Thr       1               5   - #                10  - #                15                - - Glu Asp Lys Asp Leu Gln Ser Arg Pro Phe Ty - #r Pro Lys Gln Asp Tyr                   20      - #            25      - #            30                    - - Gly Ala Tyr Gln                                                                   35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:25:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 36 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:25:                               - - Asp Tyr Gly Ala Tyr Gln His Ile Gly Asp Gl - #y Arg Gly Val Lys Tyr       1               5   - #                10  - #                15                - - Ala Ser Gly Leu Tyr Phe Asp Glu His His Ar - #g Lys Gln Arg Val Gly                   20      - #            25      - #            30                    - - Ile Glu Tyr Ile                                                                   35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:26:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 36 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:26:                               - - Gly Ile Glu Tyr Ile Tyr Glu Asn Lys Asn Ly - #s Ala Gly Ile Ile Asp       1               5   - #                10  - #                15                - - Lys Ala Val Leu Ser Ala Asn Gln Gln Asn Il - #e Ile Leu Asp Ser Tyr                   20      - #            25      - #            30                    - - Met Arg His Thr                                                                   35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:27:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 36 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:27:                               - - Asp Ser Tyr Met Arg His Thr His Cys Ser Le - #u Tyr Pro Asn Pro Ser       1               5   - #                10  - #                15                - - Lys Asn Cys Arg Pro Thr Leu Asp Lys Pro Ty - #r Ser Tyr Tyr His Ser                   20      - #            25      - #            30                    - - Asp Arg Asn Val                                                                   35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:28:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 36 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:28:                               - - Ser Asp Arg Asn Val Tyr Lys Glu Lys His As - #n Met Leu Gln Leu Asn       1               5   - #                10  - #                15                - - Leu Glu Lys Lys Ile Gln Gln Asn Trp Leu Th - #r His Gln Ile Ala Phe                   20      - #            25      - #            30                    - - Asn Leu Gly Phe                                                                   35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:29:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 36 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:29:                               - - Thr His Gln Ile Ala Phe Asn Leu Gly Phe As - #p Asp Phe Thr Ser Ala       1               5   - #                10  - #                15                - - Leu Gln His Lys Asp Tyr Leu Thr Arg Arg Va - #l Ile Ala Thr Ala Ser                   20      - #            25      - #            30                    - - Ser Ile Ser Glu                                                                   35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:30:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 37 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:30:                               - - Thr Ala Ser Ser Ile Ser Glu Lys Arg Gly Gl - #u Ala Arg Arg Asn Gly       1               5   - #                10  - #                15                - - Leu Gln Ser Ser Pro Tyr Leu Tyr Pro Thr Pr - #o Lys Ala Glu Leu Val                   20      - #            25      - #            30                    - - Gly Gly Asp Leu Cys                                                               35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:31:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 36 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:31:                               - - Leu Val Gly Gly Asp Leu Cys Asn Tyr Gln Gl - #y Lys Ser Ser Asn Tyr       1               5   - #                10  - #                15                - - Ser Asp Cys Lys Val Arg Leu Ile Lys Gly Ly - #s Asn Tyr Tyr Phe Ala                   20      - #            25      - #            30                    - - Ala Arg Asn Asn                                                                   35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:32:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 36 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:32:                               - - Phe Ala Ala Arg Asn Asn Met Ala Leu Gly Ly - #s Tyr Val Asp Leu Gly       1               5   - #                10  - #                15                - - Leu Gly Met Arg Tyr Asp Val Ser Arg Thr Ly - #s Ala Asn Glu Ser Thr                   20      - #            25      - #            30                    - - Ile Ser Val Gly                                                                   35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:33:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 36 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:33:                               - - Ser Thr Ile Ser Val Gly Lys Phe Lys Asn Ph - #e Ser Trp Asn Thr Gly       1               5   - #                10  - #                15                - - Ile Val Ile Lys Pro Thr Glu Trp Leu Asp Le - #u Ser Tyr Arg Leu Ser                   20      - #            25      - #            30                    - - Thr Gly Phe Arg                                                                   35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:34:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 36 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:34:                               - - Leu Ser Thr Gly Phe Arg Asn Pro Ser Phe Al - #a Glu Met Tyr Gly Trp       1               5   - #                10  - #                15                - - Arg Tyr Gly Gly Lys Asp Thr Asp Val Tyr Il - #e Gly Lys Phe Lys Pro                   20      - #            25      - #            30                    - - Glu Thr Ser Arg                                                                   35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:35:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 36 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:35:                               - - Lys Pro Glu Thr Ser Arg Asn Gln Glu Phe Gl - #y Leu Ala Leu Lys Gly       1               5   - #                10  - #                15                - - Asp Phe Gly Asn Ile Glu Ile Ser His Phe Se - #r Asn Ala Tyr Arg Asn                   20      - #            25      - #            30                    - - Leu Ile Ala Phe                                                                   35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:36:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 36 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:36:                        - - Tyr Arg Asn Leu Ile Ala Phe Ala Glu Glu Le - #u Ser Lys Asn Gly Thr       1               5   - #                10  - #                15                - - Thr Gly Lys Gly Asn Tyr Gly Tyr His Asn Al - #a Gln Asn Ala Lys Leu                   20      - #            25      - #            30                    - - Val Gly Val Asn                                                                   35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:37:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 36 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:37:                               - - Ala Lys Leu Val Gly Val Asn Ile Thr Ala Gl - #n Leu Asp Phe Asn Gly       1               5   - #                10  - #                15                - - Leu Trp Lys Arg Ile Pro Tyr Gly Trp Tyr Al - #a Thr Phe Ala Tyr Asn                   20      - #            25      - #            30                    - - Arg Val Lys Val                                                                   35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:38:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 36 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:38:                               - - Ala Tyr Asn Arg Val Lys Val Lys Asp Gln Ly - #s Ile Asn Ala Gly Leu       1               5   - #                10  - #                15                - - Ala Ser Val Ser Ser Tyr Leu Phe Asp Ala Il - #e Gln Pro Ser Arg Tyr                   20      - #            25      - #            30                    - - Ile Ile Gly Leu                                                                   35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:39:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 36 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:39:                               - - Ser Arg Tyr Ile Ile Gly Leu Asp Tyr Asp Hi - #s Pro Ser Asn Thr Trp       1               5   - #                10  - #                15                - - Gly Ile Lys Thr Met Phe Thr Gln Ser Lys Al - #a Lys Ser Gln Asn Glu                   20      - #            25      - #            30                    - - Leu Leu Gly Lys                                                                   35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:40:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 36 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:40:                               - - Asn Glu Leu Leu Gly Lys Arg Ala Leu Gly As - #n Asn Ser Arg Asn Val       1               5   - #                10  - #                15                - - Lys Ser Thr Arg Lys Leu Thr Arg Ala Trp Hi - #s Ile Leu Asp Val Ser                   20      - #            25      - #            30                    - - Gly Tyr Tyr Met                                                                   35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:41:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 30 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:41:                               - - Ser Gly Tyr Tyr Met Val Asn Arg Ser Ile Le - #u Phe Arg Leu Gly Val       1               5   - #                10  - #                15                - - Tyr Asn Leu Leu Asn Tyr Arg Tyr Val Thr Tr - #p Glu Ala Val                           20      - #            25      - #            30                    - -  - - (2) INFORMATION FOR SEQ ID NO:42:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 23 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:42:                               - - Leu Leu Asn Tyr Arg Tyr Val Thr Trp Glu Al - #a Val Arg Gln Thr Ala       1               5   - #                10  - #                15                - - Gln Gly Ala Glu Phe Asp Ile                                                           20                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:43:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 9 amino - #acids                                                   (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:43:                               - - Asp Asn Glu Val Thr Gly Leu Gly Lys                                       1               5                                                               - -  - - (2) INFORMATION FOR SEQ ID NO:44:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 16 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:44:                               - - Glu Gln Val Leu Asn Ile Arg Asp Leu Thr Ar - #g Tyr Asp Pro Gly Ile       1               5   - #                10  - #                15                - -  - - (2) INFORMATION FOR SEQ ID NO:45:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 35 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:45:                               - - Glu Gln Val Leu Asn Ile Arg Asp Leu Thr Ar - #g Tyr Asp Pro Gly Ile       1               5   - #                10  - #                15                - - Ser Val Val Glu Gln Gly Arg Gly Ala Ser Se - #r Gly Tyr Ser Ile Arg                   20      - #            25      - #            30                    - - Gly Met Asp                                                                       35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:46:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 19 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:46:                               - - Gly Ala Ile Asn Glu Ile Glu Tyr Glu Asn Va - #l Lys Ala Val Glu Ile       1               5   - #                10  - #                15                - - Ser Lys Gly                                                                - -  - - (2) INFORMATION FOR SEQ ID NO:47:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 7 amino - #acids                                                   (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:47:                               - - Gly Ala Leu Ala Gly Ser Val                                               1               5                                                               - -  - - (2) INFORMATION FOR SEQ ID NO:48:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 15 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:48:                               - - Ala Glu Thr Gln Ser Ile Lys Asp Thr Lys Gl - #u Ala Ile Ser Cys           1               5   - #                10  - #                15                - -  - - (2) INFORMATION FOR SEQ ID NO:49:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 14 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:49:                               - - Cys Ser Gly Gly Gly Ser Phe Asp Val Asp As - #n Val Ser Asn               1               5   - #                10                                       - -  - - (2) INFORMATION FOR SEQ ID NO:50:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 31 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:50:                               - - Leu Glu Gly Gly Phe Tyr Gly Pro Lys Gly Gl - #u Glu Leu Gly Phe Arg       1               5   - #                10  - #                15                - - Phe Leu Ala Gly Asp Lys Lys Val Phe Gly Va - #l Phe Ser Ala Lys                       20      - #            25      - #            30                    - -  - - (2) INFORMATION FOR SEQ ID NO:51:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 23 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:51:                               - - Thr Val Gly Lys Lys Thr Tyr Gln Val Glu Al - #a Cys Cys Ser Asn Leu       1               5   - #                10  - #                15                - - Ser Tyr Val Lys Phe Gly Met                                                           20                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:52:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 23 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:52:                               - - Ala Thr Val Lys Gly Ala Phe Tyr Gly Pro Ly - #s Ala Ser Glu Leu Gly       1               5   - #                10  - #                15                - - Gly Tyr Phe Thr Tyr Asn Gly                                                           20                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:53:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 35 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:53:                               - - Met Lys Leu Ala Ala Leu Asn Leu Phe Asp Ar - #g Asn Lys Pro Ser Leu       1               5   - #                10  - #                15                - - Leu Asn Glu Asp Ser Tyr Met Ile Phe Ser Se - #r Arg Ser Thr Ile Glu                   20      - #            25      - #            30                    - - Glu Asp Val                                                                       35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:54:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 35 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:54:                               - - Ser Thr Ile Glu Glu Asp Val Lys Asn Asp As - #n Gln Asn Gly Glu His       1               5   - #                10  - #                15                - - Pro Ile Asp Ser Ile Val Asp Pro Arg Ala Pr - #o Asn Ser Asn Glu Asn                   20      - #            25      - #            30                    - - Arg His Gly                                                                       35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:55:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 35 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:55:                               - - Ser Asn Glu Asn Arg His Gly Gln Lys Tyr Va - #l Tyr Ser Gly Leu Tyr       1               5   - #                10  - #                15                - - Tyr Ile Gln Ser Trp Ser Leu Arg Asp Leu Pr - #o Asn Lys Lys Phe Tyr                   20      - #            25      - #            30                    - - Ser Gly Tyr                                                                       35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:56:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 35 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:56:                               - - Lys Lys Phe Tyr Ser Gly Tyr Tyr Gly Tyr Al - #a Tyr Tyr Phe Gly Asn       1               5   - #                10  - #                15                - - Thr Thr Ala Ser Ala Leu Pro Val Gly Gly Va - #l Ala Thr Tyr Lys Gly                   20      - #            25      - #            30                    - - Thr Trp Ser                                                                       35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:57:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 35 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:57:                               - - Thr Tyr Lys Gly Thr Trp Ser Phe Ile Thr Al - #a Ala Glu Asn Gly Lys       1               5   - #                10  - #                15                - - Asn Tyr Glu Leu Leu Arg Asn Ser Gly Gly Gl - #y Gln Ala Tyr Ser Arg                   20      - #            25      - #            30                    - - Arg Ser Ala                                                                       35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:58:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 35 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:58:                               - - Ala Tyr Ser Arg Arg Ser Ala Thr Pro Glu As - #p Ile Asp Leu Asp Arg       1               5   - #                10  - #                15                - - Lys Thr Gly Leu Thr Ser Glu Phe Thr Val As - #n Phe Gly Thr Lys Lys                   20      - #            25      - #            30                    - - Leu Thr Gly                                                                       35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:59:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 35 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:59:                               - - Gly Thr Lys Lys Leu Thr Gly Gly Leu Tyr Ty - #r Asn Leu Arg Glu Thr       1               5   - #                10  - #                15                - - Asp Ala Asn Lys Ser Gln Asn Arg Thr His Ly - #s Leu Tyr Asp Leu Glu                   20      - #            25      - #            30                    - - Ala Asp Val                                                                       35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:60:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 35 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:60:                               - - Tyr Asp Leu Glu Ala Asp Val His Ser Asn Ar - #g Phe Arg Gly Lys Val       1               5   - #                10  - #                15                - - Lys Pro Thr Lys Lys Glu Ser Ser Glu Glu Hi - #s Pro Phe Thr Ser Glu                   20      - #            25      - #            30                    - - Gly Thr Leu                                                                       35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:61:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 35 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:61:                               - - Phe Thr Ser Glu Gly Thr Leu Glu Gly Gly Ph - #e Tyr Gly Pro Glu Gly       1               5   - #                10  - #                15                - - Gln Glu Leu Gly Gly Lys Phe Leu Ala His As - #p Lys Lys Val Leu Gly                   20      - #            25      - #            30                    - - Val Phe Ser                                                                       35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:62:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 35 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:62:                               - - Lys Val Leu Gly Val Phe Ser Ala Lys Glu Gl - #n Gln Glu Thr Ser Glu       1               5   - #                10  - #                15                - - Asn Lys Lys Leu Pro Lys Glu Thr Leu Ile As - #p Gly Lys Leu Thr Thr                   20      - #            25      - #            30                    - - Phe Lys Thr                                                                       35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:63:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 35 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:63:                               - - Lys Leu Thr Thr Phe Lys Thr Thr Asn Ala Th - #r Ala Asn Ala Thr Thr       1               5   - #                10  - #                15                - - Asp Ala Thr Thr Ser Thr Thr Ala Ser Thr Ly - #s Thr Asp Thr Thr Thr                   20      - #            25      - #            30                    - - Asn Ala Thr                                                                       35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:64:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 35 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:64:                               - - Asp Thr Thr Thr Asn Ala Thr Ala Asn Thr Gl - #u Asn Phe Thr Thr Lys       1               5   - #                10  - #                15                - - Asp Ile Pro Ser Leu Gly Glu Ala Asp Tyr Le - #u Leu Ile Asp Asn Tyr                   20      - #            25      - #            30                    - - Pro Val Pro                                                                       35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:65:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 35 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:65:                               - - Ile Asp Asn Tyr Pro Val Pro Leu Phe Pro Gl - #u Ser Gly Asp Phe Ile       1               5   - #                10  - #                15                - - Ser Ser Lys His His Thr Val Gly Lys Lys Th - #r Tyr Gln Val Glu Ala                   20      - #            25      - #            30                    - - Cys Cys Ser                                                                       35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:66:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 36 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:66:                               - - Cys Ser Asn Leu Ser Tyr Val Lys Phe Gly Me - #t Tyr Tyr Glu Ala Pro       1               5   - #                10  - #                15                - - Pro Lys Glu Glu Glu Lys Glu Lys Glu Lys As - #p Lys Asp Lys Glu Lys                   20      - #            25      - #            30                    - - Glu Lys Gln Ala                                                                   35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:67:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 35 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:67:                               - - Lys Glu Lys Asp Lys Asp Lys Glu Lys Glu Ly - #s Gln Ala Thr Thr Ser       1               5   - #                10  - #                15                - - Ile Lys Thr Tyr Tyr Gln Phe Leu Leu Gly Le - #u Arg Thr Pro Ser Ser                   20      - #            25      - #            30                    - - Glu Ile Pro                                                                       35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:68:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 35 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:68:                               - - Thr Pro Ser Ser Glu Ile Pro Lys Glu Gly Se - #r Ala Lys Tyr His Gly       1               5   - #                10  - #                15                - - Asn Trp Phe Gly Tyr Ile Ser Asp Gly Glu Th - #r Ser Tyr Ser Ala Ser                   20      - #            25      - #            30                    - - Gly Asp Lys                                                                       35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:69:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 35 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:69:                               - - Tyr Ser Ala Ser Gly Asp Lys Glu Arg Ser Ly - #s Asn Ala Val Ala Glu       1               5   - #                10  - #                15                - - Phe Asn Val Asn Phe Ala Glu Lys Thr Leu Th - #r Gly Glu Leu Lys Arg                   20      - #            25      - #            30                    - - His Asp Thr                                                                       35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:70:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 35 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:70:                               - - Glu Leu Lys Arg His Asp Thr Gln Asn Pro Va - #l Phe Lys Ile Asn Ala       1               5   - #                10  - #                15                - - Thr Phe Gln Ser Gly Lys Asn Asp Phe Thr Gl - #y Thr Ala Thr Ala Lys                   20      - #            25      - #            30                    - - Asp Leu Ala                                                                       35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:71:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 35 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:71:                               - - Ala Thr Ala Lys Asp Leu Ala Ile Asp Gly Ly - #s Asn Thr Gln Gly Thr       1               5   - #                10  - #                15                - - Ser Lys Val Asn Phe Thr Ala Thr Val Asn Gl - #y Ala Phe Tyr Gly Pro                   20      - #            25      - #            30                    - - His Ala Thr                                                                       35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:72:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 26 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:72:                               - - Phe Tyr Gly Pro His Ala Thr Glu Leu Gly Gl - #y Tyr Phe Thr Tyr Asn       1               5   - #                10  - #                15                - - Gly Asn Asn Pro Thr Asp Lys Asn Ser Ser                                               20      - #            25                                           - -  - - (2) INFORMATION FOR SEQ ID NO:73:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 31 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:73:                               - - Cys Pro Thr Asp Lys Asn Ser Ser Ser Asn Se - #r Glu Lys Ala Arg Ala       1               5   - #                10  - #                15                - - Ala Val Val Phe Gly Ala Lys Lys Gln Gln Va - #l Glu Thr Thr Lys                       20      - #            25      - #            30                    - -  - - (2) INFORMATION FOR SEQ ID NO:74:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 8 amino - #acids                                                   (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:74:                               - - Leu Glu Gly Gly Phe Tyr Gly Pro                                           1               5                                                               - -  - - (2) INFORMATION FOR SEQ ID NO:75:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 8 amino - #acids                                                   (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:75:                               - - Cys Ser Gly Gly Gly Ser Phe Asp                                           1               5                                                               - -  - - (2) INFORMATION FOR SEQ ID NO:76:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 6 amino - #acid                                                    (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:76:                               - - Tyr Val Tyr Ser Gly Leu                                                   1               5                                                               - -  - - (2) INFORMATION FOR SEQ ID NO:77:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 11 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:77:                               - - Cys Cys Ser Asn Leu Ser Tyr Val Lys Phe Gl - #y                           1               5   - #                10                                       - -  - - (2) INFORMATION FOR SEQ ID NO:78:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 7 amino - #acids                                                   (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:78:                               - - Phe Leu Leu Gly His Arg Thr                                               1               5                                                               - -  - - (2) INFORMATION FOR SEQ ID NO:79:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 6 amino - #acids                                                   (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:79:                               - - Glu Phe Asn Val Asp Phe                                                   1               5                                                               - -  - - (2) INFORMATION FOR SEQ ID NO:80:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 7 amino - #acids                                                   (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:80:                               - - Asn Ala Phe Thr Gly Thr Ala                                               1               5                                                               - -  - - (2) INFORMATION FOR SEQ ID NO:81:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 7 amino - #acids                                                   (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:81:                               - - Val Asn Gly Ala Phe Tyr Gly                                               1               5                                                               - -  - - (2) INFORMATION FOR SEQ ID NO:82:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 6 amino - #acids                                                   (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:82:                               - - Glu Leu Gly Gly Tyr Phe                                                   1               5                                                               - -  - - (2) INFORMATION FOR SEQ ID NO:83:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 6 amino - #acids                                                   (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:83:                               - - Val Val Phe Gly Ala Arg                                                   1               5                                                               - -  - - (2) INFORMATION FOR SEQ ID NO:84:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 6 amino - #acids                                                   (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:84:                               - - Val Val Phe Gly Ala Lys                                                   1               5                                                               - -  - - (2) INFORMATION FOR SEQ ID NO:85:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 7 amino - #acids                                                   (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:85:                               - - Leu Glu Gly Gly Phe Tyr Gly                                               1               5                                                               - -  - - (2) INFORMATION FOR SEQ ID NO:86:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 103 base - #pairs                                                  (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:86:                               - - TATGGAAACT CAAAGTATAA AAGATACAAA AGAAGCTATA TCATCTGAAG TG -              #GACACTCA     60                                                                  - - AAGTACAGAA GATTCAGAAT TAGAAACTAT CTCAGTCACT GCA    - #                       - #103                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:87:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 97 base - #pairs                                                   (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:87:                               - - ACCTTTGAGT TTCATATTTT CTATGTTTTC TTCGATATAG TAGACTTCAC CT -              #GTGAGTTT     60                                                                  - - CATGTCTTCT AAGTCTTAAT CTTTGATAGA GTCAGTG      - #                       - #      97                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:88:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 115 base - #pairs                                                  (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:88:                               - - TATGAAAGCT ACTAAACTGG TTCTGGGTGC TGTTATCCTG GGTTCCACTC TG -              #CTGGCTGG     60                                                                  - - TTGTAGCGGA GGTGGTTGTT TTGATGTAGA TAACGTCTCT AATACCCCCT CT - #TCT              115                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:89:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 116 base - #pairs                                                  (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:89:                               - - ACTTTCGATG ATTTGACCAA GACCCACGAC AATAGGACCC AAGGTGAGAC GA -              #CCGACCAA     60                                                                  - - CATCGCCTCC ACCAACAAAA CTACATCTAT TGCAGAGATT ATGGGGGAGA AG - #ATTT             116                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:90:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 109 base - #pairs                                                  (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:90:                               - - TATGCGATAT CTGGCAACAT TGTTGTTATC TCTGGCGGTG TTAATCACCG CT -              #GGTTGTAG     60                                                                  - - CGGAGGTGGT TCTTTTGATG TAGATAACGT CTCTAATACC CCCTCTTCT  - #                   109                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:91:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 110 base - #pairs                                                  (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:91:                               - - ACGCTATAGA CCGTTGTAAC AACAATAGAG ACCGCCACAA TTAGTGGCGA CC -              #AACATCGC     60                                                                  - - CTCCACCAAG AAAACTACAT CTATTGCAGA GATTATGGGG GAGAAGATTT  - #                  110                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:92:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 117 base - #pairs                                                  (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:92:                               - - TATGCAACTG AACAAAGTGC TGAAAGGGCT GATGATTGCT CTGCCTGTTA TG -              #GCAATGCT     60                                                                  - - GGTTGTAGCG GAGGTGGTTC TTTTGATGTA GATAACGTCT CTAATACCCC CT - #CTTCT            117                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:93:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 119 base - #pairs                                                  (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:93:                               - - ACGTTGACTT GTTTCACGAC TTTCCCGACT ACTAACGAGA CGGACAATAC CG -              #TTAACGAC     60                                                                  - - CAACATCGCC TCCACCAAGA AAACTACATC TATTGCAGAG ATTATGGGGG AG -             #AAGATTT     119                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:94:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 908 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:94:                               - - Met Gln Gln Gln His Leu Phe Arg Leu Asn Il - #e Leu Cys Leu Ser         Leu                                                                              1               5   - #                10  - #                15               - - Met Thr Ala Leu Pro Val Tyr Ala Glu Asn Va - #l Gln Ala Glu Gln Ala                   20      - #            25      - #            30                    - - Gln Glu Lys Gln Leu Asp Thr Ile Gln Val Ly - #s Ala Lys Lys Gln Lys               35          - #        40          - #        45                        - - Thr Arg Arg Asp Asn Glu Val Thr Gly Leu Gl - #y Lys Leu Val Lys Ser           50              - #    55              - #    60                            - - Ser Asp Thr Leu Ser Lys Glu Gln Val Leu As - #n Ile Arg Asp Leu Thr       65                  - #70                  - #75                  - #80         - - Arg Tyr Asp Pro Gly Ile Ala Val Val Glu Gl - #n Gly Arg Gly Ala Ser                       85  - #                90  - #                95                - - Ser Gly Tyr Ser Ile Arg Gly Met Asp Lys As - #n Arg Val Ser Leu Thr                   100      - #           105      - #           110                   - - Val Asp Gly Val Ser Gln Ile Gln Ser Tyr Th - #r Ala Gln Ala Ala Leu               115          - #       120          - #       125                       - - Gly Gly Thr Arg Thr Ala Gly Ser Ser Gly Al - #a Ile Asn Glu Ile Glu           130              - #   135              - #   140                           - - Tyr Glu Asn Val Lys Ala Val Glu Ile Ser Ly - #s Gly Ser Asn Ser Ser       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Glu Tyr Gly Asn Gly Ala Leu Ala Gly Ser Va - #l Ala Phe Gln Thr         Lys                                                                                              165  - #               170  - #               175              - - Thr Ala Ala Asp Ile Ile Gly Glu Gly Lys Gl - #n Trp Gly Ile Gln Ser                   180      - #           185      - #           190                   - - Lys Thr Ala Tyr Ser Gly Lys Asp His Ala Le - #u Thr Gln Ser Leu Ala               195          - #       200          - #       205                       - - Leu Ala Gly Arg Ser Gly Gly Ala Glu Ala Le - #u Leu Ile Tyr Thr Lys           210              - #   215              - #   220                           - - Arg Arg Gly Arg Glu Ile His Ala His Lys As - #p Ala Gly Lys Gly Val       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Gln Ser Phe Asn Arg Leu Val Leu Asp Glu As - #p Lys Lys Glu Gly         Gly                                                                                              245  - #               250  - #               255              - - Ser Gln Tyr Arg Tyr Phe Ile Val Glu Glu Gl - #u Cys His Asn Gly Tyr                   260      - #           265      - #           270                   - - Ala Ala Cys Lys Asn Lys Leu Lys Glu Asp Al - #a Ser Val Lys Asp Glu               275          - #       280          - #       285                       - - Arg Lys Thr Val Ser Thr Gln Asp Tyr Thr Gl - #y Ser Asn Arg Leu Leu           290              - #   295              - #   300                           - - Ala Asn Pro Leu Glu Tyr Gly Ser Gln Ser Tr - #p Leu Phe Arg Pro Gly       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Trp His Leu Asp Asn Arg His Tyr Val Gly Al - #a Val Leu Glu Arg         Thr                                                                                              325  - #               330  - #               335              - - Gln Gln Thr Phe Asp Thr Arg Asp Met Thr Va - #l Pro Ala Tyr Phe Thr                   340      - #           345      - #           350                   - - Ser Glu Asp Tyr Val Pro Gly Ser Leu Lys Gl - #y Leu Gly Lys Tyr Ser               355          - #       360          - #       365                       - - Gly Asp Asn Lys Ala Glu Arg Leu Phe Val Gl - #n Gly Glu Gly Ser Thr           370              - #   375              - #   380                           - - Leu Gln Gly Ile Gly Tyr Gly Thr Gly Val Ph - #e Tyr Asp Glu Arg His       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Thr Lys Asn Arg Tyr Gly Val Glu Tyr Val Ty - #r His Asn Ala Asp         Lys                                                                                              405  - #               410  - #               415              - - Asp Thr Trp Ala Asp Tyr Ala Arg Leu Ser Ty - #r Asp Arg Gln Gly Ile                   420      - #           425      - #           430                   - - Asp Leu Asp Asn Arg Leu Gln Gln Thr His Cy - #s Ser His Asp Gly Ser               435          - #       440          - #       445                       - - Asp Lys Asn Cys Arg Pro Asp Gly Asn Lys Pr - #o Tyr Ser Phe Tyr Lys           450              - #   455              - #   460                           - - Ser Asp Arg Met Ile Tyr Glu Glu Ser Arg As - #n Leu Phe Gln Ala Val       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Phe Lys Lys Ala Phe Asp Thr Ala Lys Ile Ar - #g His Asn Leu Ser         Ile                                                                                              485  - #               490  - #               495              - - Asn Leu Gly Tyr Asp Arg Phe Lys Ser Gln Le - #u Ser His Ser Asp Tyr                   500      - #           505      - #           510                   - - Tyr Leu Gln Asn Ala Val Gln Ala Tyr Asp Le - #u Ile Thr Pro Lys Lys               515          - #       520          - #       525                       - - Pro Pro Phe Pro Asn Gly Ser Lys Asp Asn Pr - #o Tyr Arg Val Ser Ile           530              - #   535              - #   540                           - - Gly Lys Thr Thr Val Asn Thr Ser Pro Ile Cy - #s Arg Phe Gly Asn Asn       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Thr Tyr Thr Asp Cys Thr Pro Arg Asn Ile Gl - #y Gly Asn Gly Tyr         Tyr                                                                                              565  - #               570  - #               575              - - Ala Ala Val Gln Asp Asn Val Arg Leu Gly Ar - #g Trp Ala Asp Val Gly                   580      - #           585      - #           590                   - - Ala Gly Ile Arg Tyr Asp Tyr Arg Ser Thr Hi - #s Ser Glu Asp Lys Ser               595          - #       600          - #       605                       - - Val Ser Thr Gly Thr His Arg Asn Leu Ser Tr - #p Asn Ala Gly Val Val           610              - #   615              - #   620                           - - Leu Lys Pro Phe Thr Trp Met Asp Leu Thr Ty - #r Arg Ala Ser Thr Gly       625                 6 - #30                 6 - #35                 6 -       #40                                                                               - - Phe Arg Leu Pro Ser Phe Ala Glu Met Tyr Gl - #y Trp Arg Ala Gly         Glu                                                                                              645  - #               650  - #               655              - - Ser Leu Lys Thr Leu Asp Leu Lys Pro Glu Ly - #s Ser Phe Asn Arg Glu                   660      - #           665      - #           670                   - - Ala Gly Ile Val Phe Lys Gly Asp Phe Gly As - #n Leu Glu Ala Ser Tyr               675          - #       680          - #       685                       - - Phe Asn Asn Ala Tyr Arg Asp Leu Ile Ala Ph - #e Gly Tyr Glu Thr Arg           690              - #   695              - #   700                           - - Thr Gln Asn Gly Gln Thr Ser Ala Ser Gly As - #p Pro Gly Tyr Arg Asn       705                 7 - #10                 7 - #15                 7 -       #20                                                                               - - Ala Gln Asn Ala Arg Ile Ala Gly Ile Asn Il - #e Leu Gly Lys Ile         Asp                                                                                              725  - #               730  - #               735              - - Trp His Gly Val Trp Gly Gly Leu Pro Asp Gl - #y Leu Tyr Ser Thr Leu                   740      - #           745      - #           750                   - - Ala Tyr Asn Arg Ile Lys Val Lys Asp Ala As - #p Ile Arg Ala Asp Arg               755          - #       760          - #       765                       - - Thr Phe Val Thr Ser Tyr Leu Phe Asp Ala Va - #l Gln Pro Ser Arg Tyr           770              - #   775              - #   780                           - - Val Leu Gly Leu Gly Tyr Asp His Pro Asp Gl - #y Ile Trp Gly Ile Asn       785                 7 - #90                 7 - #95                 8 -       #00                                                                               - - Thr Met Phe Thr Tyr Ser Lys Ala Lys Ser Va - #l Asp Glu Leu Leu         Gly                                                                                              805  - #               810  - #               815              - - Ser Gln Ala Leu Leu Asn Gly Asn Ala Asn Al - #a Lys Lys Ala Ala Ser                   820      - #           825      - #           830                   - - Arg Arg Thr Arg Pro Trp Tyr Val Thr Asp Va - #l Ser Gly Tyr Tyr Asn               835          - #       840          - #       845                       - - Ile Lys Lys His Leu Thr Leu Arg Ala Gly Va - #l Tyr Asn Leu Leu Asn           850              - #   855              - #   860                           - - Tyr Arg Tyr Val Thr Trp Glu Asn Val Arg Gl - #n Thr Ala Gly Gly Ala       865                 8 - #70                 8 - #75                 8 -       #80                                                                               - - Val Asn Gln His Lys Asn Val Gly Val Tyr As - #n Arg Tyr Ala Ala         Pro                                                                                              885  - #               890  - #               895              - - Gly Arg Asn Tyr Thr Phe Ser Leu Glu Met Ly - #s Phe                                   900      - #           905                                          - -  - - (2) INFORMATION FOR SEQ ID NO:95:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 911 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:95:                               - - Met Gln Gln Gln His Leu Phe Arg Leu Asn Il - #e Leu Cys Leu Ser Leu       1               5   - #                10  - #                15                - - Met Thr Ala Leu Pro Ala Tyr Ala Glu Asn Va - #l Gln Ala Gly Gln Ala                   20      - #            25      - #            30                    - - Gln Glu Lys Gln Leu Asp Thr Ile Gln Val Ly - #s Ala Lys Lys Gln Lys               35          - #        40          - #        45                        - - Thr Arg Arg Asp Asn Glu Val Thr Gly Leu Gl - #y Lys Leu Val Lys Thr           50              - #    55              - #    60                            - - Ala Asp Thr Leu Ser Lys Glu Gln Val Leu As - #p Ile Arg Asp Leu Thr       65                  - #70                  - #75                  - #80         - - Arg Tyr Asp Pro Gly Ile Ala Val Val Glu Gl - #n Gly Arg Gly Ala Ser                       85  - #                90  - #                95                - - Ser Gly Tyr Ser Ile Arg Gly Met Asp Lys As - #n Arg Val Ser Leu Thr                   100      - #           105      - #           110                   - - Val Asp Gly Leu Ala Gln Ile Gln Ser Tyr Th - #r Ala Gln Ala Ala Leu               115          - #       120          - #       125                       - - Gly Gly Thr Arg Thr Ala Gly Ser Ser Gly Al - #a Ile Asn Glu Ile Glu           130              - #   135              - #   140                           - - Tyr Glu Asn Val Lys Ala Val Glu Ile Ser Ly - #s Gly Ser Asn Ser Val       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Glu Gln Gly Ser Gly Ala Leu Ala Gly Ser Va - #l Ala Phe Gln Thr         Lys                                                                                              165  - #               170  - #               175              - - Thr Ala Asp Asp Val Ile Gly Glu Gly Arg Gl - #n Trp Gly Ile Gln Ser                   180      - #           185      - #           190                   - - Lys Thr Ala Tyr Ser Gly Lys Asn Arg Gly Le - #u Thr Gln Ser Ile Ala               195          - #       200          - #       205                       - - Leu Ala Gly Arg Ile Gly Gly Ala Glu Ala Le - #u Leu Ile His Thr Gly           210              - #   215              - #   220                           - - Arg Arg Ala Gly Glu Ile Arg Ala His Glu As - #p Ala Gly Arg Gly Val       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Gln Ser Phe Asn Arg Leu Val Pro Val Glu As - #p Ser Ser Glu Tyr         Ala                                                                                              245  - #               250  - #               255              - - Tyr Phe Ile Val Glu Asp Glu Cys Glu Gly Ly - #s Asn Tyr Glu Thr Cys                   260      - #           265      - #           270                   - - Lys Ser Lys Pro Lys Lys Asp Val Val Gly Ly - #s Asp Glu Arg Gln Thr               275          - #       280          - #       285                       - - Val Ser Thr Arg Asp Tyr Thr Gly Pro Asn Ar - #g Phe Leu Ala Asp Pro           290              - #   295              - #   300                           - - Leu Ser Tyr Glu Ser Arg Ser Trp Leu Phe Ar - #g Pro Gly Phe Arg Phe       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Glu Asn Lys Arg His Tyr Ile Gly Gly Ile Le - #u Glu His Thr Gln         Gln                                                                                              325  - #               330  - #               335              - - Thr Phe Asp Thr Arg Asp Met Thr Val Pro Al - #a Phe Leu Thr Lys Ala                   340      - #           345      - #           350                   - - Val Phe Asp Ala Asn Ser Lys Gln Ala Gly Se - #r Leu Pro Gly Asn Gly               355          - #       360          - #       365                       - - Lys Tyr Ala Gly Asn His Lys Tyr Gly Gly Le - #u Phe Thr Asn Gly Glu           370              - #   375              - #   380                           - - Asn Gly Ala Leu Val Gly Ala Glu Tyr Gly Th - #r Gly Val Phe Tyr Asp       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Glu Thr His Thr Lys Ser Arg Tyr Gly Leu Gl - #u Tyr Val Tyr Thr         Asn                                                                                              405  - #               410  - #               415              - - Ala Asp Lys Asp Thr Trp Ala Asp Tyr Ala Ar - #g Leu Ser Tyr Asp Arg                   420      - #           425      - #           430                   - - Gln Gly Ile Gly Leu Asp Asn His Phe Gln Gl - #n Thr His Cys Ser Ala               435          - #       440          - #       445                       - - Asp Gly Ser Asp Lys Tyr Cys Arg Pro Ser Al - #a Asp Lys Pro Phe Ser           450              - #   455              - #   460                           - - Tyr Tyr Lys Ser Asp Arg Val Ile Tyr Gly Gl - #u Ser His Arg Leu Leu       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Gln Ala Ala Phe Lys Lys Ser Phe Asp Thr Al - #a Lys Ile Arg His         Asn                                                                                              485  - #               490  - #               495              - - Leu Ser Val Asn Leu Gly Phe Asp Arg Phe As - #p Ser Asn Leu Arg His                   500      - #           505      - #           510                   - - Gln Asp Tyr Tyr Tyr Gln His Ala Asn Arg Al - #a Tyr Ser Ser Lys Thr               515          - #       520          - #       525                       - - Pro Pro Lys Thr Ala Asn Pro Asn Gly Asp Ly - #s Ser Lys Pro Tyr Trp           530              - #   535              - #   540                           - - Val Ser Ile Gly Gly Gly Asn Val Val Thr Gl - #y Gln Ile Cys Leu Phe       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Gly Asn Asn Thr Tyr Thr Asp Cys Thr Pro Ar - #g Ser Ile Asn Gly         Lys                                                                                              565  - #               570  - #               575              - - Ser Tyr Tyr Ala Ala Val Arg Asp Asn Val Ar - #g Leu Gly Arg Trp Ala                   580      - #           585      - #           590                   - - Asp Val Gly Ala Gly Leu Arg Tyr Asp Tyr Ar - #g Ser Thr His Ser Asp               595          - #       600          - #       605                       - - Asp Gly Ser Val Ser Thr Gly Thr His Arg Th - #r Leu Ser Trp Asn Ala           610              - #   615              - #   620                           - - Gly Ile Val Leu Lys Pro Ala Asp Trp Leu As - #p Leu Thr Tyr Arg Thr       625                 6 - #30                 6 - #35                 6 -       #40                                                                               - - Ser Thr Gly Phe Arg Leu Pro Ser Phe Ala Gl - #u Met Tyr Gly Trp         Arg                                                                                              645  - #               650  - #               655              - - Ser Gly Val Gln Ser Lys Ala Val Lys Ile As - #p Pro Glu Lys Ser Phe                   660      - #           665      - #           670                   - - Asn Lys Glu Ala Gly Ile Val Phe Lys Gly As - #p Phe Gly Asn Leu Glu               675          - #       680          - #       685                       - - Ala Ser Trp Phe Asn Asn Ala Tyr Arg Asp Le - #u Ile Val Arg Gly Tyr           690              - #   695              - #   700                           - - Glu Ala Gln Ile Lys Asn Gly Lys Glu Glu Al - #a Lys Gly Asp Pro Ala       705                 7 - #10                 7 - #15                 7 -       #20                                                                               - - Tyr Leu Asn Ala Gln Ser Ala Arg Ile Thr Gl - #y Ile Asn Ile Leu         Gly                                                                                              725  - #               730  - #               735              - - Lys Ile Asp Trp Asn Gly Val Trp Asp Lys Le - #u Pro Glu Gly Trp Tyr                   740      - #           745      - #           750                   - - Ser Thr Phe Ala Tyr Asn Arg Val His Val Ar - #g Asp Ile Lys Lys Arg               755          - #       760          - #       765                       - - Ala Asp Arg Thr Asp Ile Gln Ser His Leu Ph - #e Asp Ala Ile Gln Pro           770              - #   775              - #   780                           - - Ser Arg Tyr Val Val Gly Leu Gly Tyr Asp Gl - #n Pro Glu Gly Lys Trp       785                 7 - #90                 7 - #95                 8 -       #00                                                                               - - Gly Val Asn Gly Met Leu Thr Tyr Ser Lys Al - #a Lys Glu Ile Thr         Glu                                                                                              805  - #               810  - #               815              - - Leu Leu Gly Ser Arg Ala Leu Leu Asn Gly As - #n Ser Arg Asn Thr Lys                   820      - #           825      - #           830                   - - Ala Thr Ala Arg Arg Thr Arg Pro Trp Tyr Il - #e Val Asp Val Ser Gly               835          - #       840          - #       845                       - - Tyr Tyr Thr Ile Lys Lys His Phe Thr Leu Ar - #g Ala Gly Val Tyr Asn           850              - #   855              - #   860                           - - Leu Leu Asn Tyr Arg Tyr Val Thr Trp Glu As - #n Val Arg Gln Thr Ala       865                 8 - #70                 8 - #75                 8 -       #80                                                                               - - Gly Gly Ala Val Asn Gln His Lys Asn Val Gl - #y Val Tyr Asn Arg         Tyr                                                                                              885  - #               890  - #               895              - - Ala Ala Pro Gly Arg Asn Tyr Thr Phe Ser Le - #u Glu Met Lys Phe                       900      - #           905      - #           910                   - -  - - (2) INFORMATION FOR SEQ ID NO:96:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 915 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:96:                               - - Met Gln Gln Gln His Leu Phe Arg Leu Asn Il - #e Leu Cys Leu Ser Leu       1               5   - #                10  - #                15                - - Met Thr Ala Leu Pro Ala Tyr Ala Glu Asn Va - #l Gln Ala Gly Gln Ala                   20      - #            25      - #            30                    - - Gln Glu Lys Gln Leu Asp Thr Ile Gln Val Ly - #s Ala Lys Lys Gln Lys               35          - #        40          - #        45                        - - Thr Arg Arg Asp Asn Glu Val Thr Gly Leu Gl - #y Lys Leu Val Lys Thr           50              - #    55              - #    60                            - - Ala Asp Thr Leu Ser Lys Glu Gln Val Leu As - #p Ile Arg Asp Leu Thr       65                  - #70                  - #75                  - #80         - - Arg Tyr Asp Pro Gly Ile Ala Val Val Glu Gl - #n Gly Arg Gly Ala Ser                       85  - #                90  - #                95                - - Ser Gly Tyr Ser Ile Arg Gly Met Asp Lys As - #n Arg Val Ser Leu Thr                   100      - #           105      - #           110                   - - Val Asp Gly Leu Ala Gln Ile Gln Ser Tyr Th - #r Ala Gln Ala Ala Leu               115          - #       120          - #       125                       - - Gly Gly Thr Arg Thr Ala Gly Ser Ser Gly Al - #a Ile Asn Glu Ile Glu           130              - #   135              - #   140                           - - Tyr Glu Asn Val Lys Ala Val Glu Ile Ser Ly - #s Gly Ser Asn Ser Val       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Glu Gln Gly Ser Gly Ala Leu Ala Gly Ser Va - #l Ala Phe Gln Thr         Lys                                                                                              165  - #               170  - #               175              - - Thr Ala Asp Asp Val Ile Gly Glu Gly Arg Gl - #n Trp Gly Ile Gln Ser                   180      - #           185      - #           190                   - - Lys Thr Ala Tyr Ser Gly Lys Asn Arg Gly Le - #u Thr Gln Ser Ile Ala               195          - #       200          - #       205                       - - Leu Ala Gly Arg Ile Gly Gly Ala Glu Ala Le - #u Leu Ile Arg Thr Gly           210              - #   215              - #   220                           - - Arg His Ala Gly Glu Ile Arg Ala His Glu Al - #a Ala Gly Arg Gly Val       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Gln Ser Phe Asn Arg Leu Ala Pro Val Asp As - #p Gly Ser Lys Tyr         Ala                                                                                              245  - #               250  - #               255              - - Tyr Phe Ile Val Glu Glu Glu Cys Lys Asn Gl - #y Gly His Glu Lys Cys                   260      - #           265      - #           270                   - - Lys Ala Asn Pro Lys Lys Asp Val Val Gly Gl - #u Asp Lys Arg Gln Thr               275          - #       280          - #       285                       - - Val Ser Thr Arg Asp Tyr Thr Gly Pro Asn Ar - #g Phe Leu Ala Asp Pro           290              - #   295              - #   300                           - - Leu Ser Tyr Glu Ser Arg Ser Trp Leu Phe Ar - #g Pro Gly Phe Arg Phe       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Glu Asn Lys Arg His Tyr Ile Gly Gly Ile Le - #u Glu Arg Thr Gln         Gln                                                                                              325  - #               330  - #               335              - - Thr Phe Asp Thr Arg Asp Met Thr Val Pro Al - #a Phe Leu Thr Lys Ala                   340      - #           345      - #           350                   - - Val Phe Asp Ala Asn Gln Lys Gln Ala Gly Se - #r Leu Arg Gly Asn Gly               355          - #       360          - #       365                       - - Lys Tyr Ala Gly Asn His Lys Tyr Gly Gly Le - #u Phe Thr Ser Gly Glu           370              - #   375              - #   380                           - - Asn Asn Ala Pro Val Gly Ala Glu Tyr Gly Th - #r Gly Val Phe Tyr Asp       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Glu Thr His Thr Lys Ser Arg Tyr Gly Leu Gl - #u Tyr Val Tyr Thr         Asn                                                                                              405  - #               410  - #               415              - - Ala Asp Lys Asp Thr Trp Ala Asp Tyr Ala Ar - #g Leu Ser Tyr Asp Arg                   420      - #           425      - #           430                   - - Gln Gly Ile Gly Leu Asp Asn His Phe Gln Gl - #n Thr His Cys Ser Ala               435          - #       440          - #       445                       - - Asp Gly Ser Asp Lys Tyr Cys Arg Pro Ser Al - #a Asp Lys Pro Phe Ser           450              - #   455              - #   460                           - - Tyr Tyr Lys Ser Asp Arg Val Ile Tyr Gly Gl - #u Ser His Lys Leu Leu       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Gln Ala Ala Phe Lys Lys Ser Phe Asp Thr Al - #a Lys Ile Arg His         Asn                                                                                              485  - #               490  - #               495              - - Leu Ser Val Asn Leu Gly Tyr Asp Arg Phe Gl - #y Ser Asn Leu Arg His                   500      - #           505      - #           510                   - - Gln Asp Tyr Tyr Tyr Gln Ser Ala Asn Arg Al - #a Tyr Ser Leu Lys Thr               515          - #       520          - #       525                       - - Pro Pro Gln Asn Asn Gly Lys Lys Thr Ser Pr - #o Asn Gly Arg Glu Lys           530              - #   535              - #   540                           - - Asn Pro Tyr Trp Val Ser Ile Gly Arg Gly As - #n Val Val Thr Arg Gln       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Ile Cys Leu Phe Gly Asn Asn Thr Tyr Thr As - #p Cys Thr Pro Arg         Ser                                                                                              565  - #               570  - #               575              - - Ile Asn Gly Lys Ser Tyr Tyr Ala Ala Val Ar - #g Asp Asn Val Arg Leu                   580      - #           585      - #           590                   - - Gly Arg Trp Ala Asp Val Gly Ala Gly Leu Ar - #g Tyr Asp Tyr Arg Ser               595          - #       600          - #       605                       - - Thr His Ser Asp Asp Gly Ser Val Ser Thr Gl - #y Thr His Arg Thr Leu           610              - #   615              - #   620                           - - Ser Trp Asn Ala Gly Ile Val Leu Lys Pro Al - #a Asp Trp Leu Asp Leu       625                 6 - #30                 6 - #35                 6 -       #40                                                                               - - Thr Tyr Arg Thr Ser Thr Gly Phe Arg Leu Pr - #o Ser Phe Ala Glu         Met                                                                                              645  - #               650  - #               655              - - Tyr Gly Trp Arg Ser Gly Asp Lys Ile Lys Al - #a Val Lys Ile Asp Pro                   660      - #           665      - #           670                   - - Glu Lys Ser Phe Asn Lys Glu Ala Gly Ile Va - #l Phe Lys Gly Asp Phe               675          - #       680          - #       685                       - - Gly Asn Leu Glu Ala Ser Trp Phe Asn Asn Al - #a Tyr Arg Asp Leu Ile           690              - #   695              - #   700                           - - Val Arg Gly Tyr Glu Ala Gln Ile Lys Asp Gl - #y Lys Glu Gln Val Lys       705                 7 - #10                 7 - #15                 7 -       #20                                                                               - - Gly Asn Pro Ala Tyr Leu Asn Ala Gln Ser Al - #a Arg Ile Thr Gly         Ile                                                                                              725  - #               730  - #               735              - - Asn Ile Leu Gly Lys Ile Asp Trp Asn Gly Va - #l Trp Asp Lys Leu Pro                   740      - #           745      - #           750                   - - Glu Gly Trp Tyr Ser Thr Phe Ala Tyr Asn Ar - #g Val Arg Val Arg Asp               755          - #       760          - #       765                       - - Ile Lys Lys Arg Ala Asp Arg Thr Asp Ile Gl - #n Ser His Leu Phe Asp           770              - #   775              - #   780                           - - Ala Ile Gln Pro Ser Arg Tyr Val Val Gly Se - #r Gly Tyr Asp Gln Pro       785                 7 - #90                 7 - #95                 8 -       #00                                                                               - - Glu Gly Lys Trp Gly Val Asn Gly Met Leu Th - #r Tyr Ser Lys Ala         Lys                                                                                              805  - #               810  - #               815              - - Glu Ile Thr Glu Leu Leu Gly Ser Arg Ala Le - #u Leu Asn Gly Asn Ser                   820      - #           825      - #           830                   - - Arg Asn Thr Lys Ala Thr Ala Arg Arg Thr Ar - #g Pro Trp Tyr Ile Val               835          - #       840          - #       845                       - - Asp Val Ser Gly Tyr Tyr Thr Val Lys Lys Hi - #s Phe Thr Leu Arg Ala           850              - #   855              - #   860                           - - Gly Val Tyr Asn Leu Leu Asn His Arg Tyr Va - #l Thr Trp Glu Asn Val       865                 8 - #70                 8 - #75                 8 -       #80                                                                               - - Arg Gln Thr Ala Ala Gly Ala Val Asn Gln Hi - #s Lys Asn Val Gly         Val                                                                                              885  - #               890  - #               895              - - Tyr Asn Arg Tyr Ala Ala Pro Gly Arg Asn Ty - #r Thr Phe Ser Leu Glu                   900      - #           905      - #           910                   - - Met Lys Phe                                                                       915                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:97:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 598 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:97:                               - - Met Asn Asn Pro Leu Val Asn Gln Ala Ala Me - #t Val Leu Pro Val Phe       1               5   - #                10  - #                15                - - Leu Leu Ser Ala Cys Leu Gly Gly Gly Gly Se - #r Phe Asp Leu Asp Ser                   20      - #            25      - #            30                    - - Val Glu Thr Val Gln Asp Met His Ser Lys Pr - #o Lys Tyr Glu Asp Glu               35          - #        40          - #        45                        - - Lys Ser Gln Pro Glu Ser Gln Gln Asp Val Se - #r Glu Asn Ser Gly Ala           50              - #    55              - #    60                            - - Ala Tyr Gly Phe Ala Val Lys Leu Pro Arg Ar - #g Asn Ala His Phe Asn       65                  - #70                  - #75                  - #80         - - Pro Lys Tyr Lys Glu Lys His Lys Pro Leu Gl - #y Ser Met Asp Trp Lys                       85  - #                90  - #                95                - - Lys Leu Gln Arg Gly Glu Pro Asn Ser Phe Se - #r Glu Arg Asp Glu Leu                   100      - #           105      - #           110                   - - Glu Lys Lys Arg Gly Ser Ser Glu Leu Ile Gl - #u Ser Lys Trp Glu Asp               115          - #       120          - #       125                       - - Gly Gln Ser Arg Val Val Gly Tyr Thr Asn Ph - #e Thr Tyr Val Arg Ser           130              - #   135              - #   140                           - - Gly Tyr Val Tyr Leu Asn Lys Asn Asn Ile As - #p Ile Lys Asn Asn Ile       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Val Leu Phe Gly Pro Asp Gly Tyr Leu Tyr Ty - #r Lys Gly Lys Glu         Pro                                                                                              165  - #               170  - #               175              - - Ser Lys Glu Leu Pro Ser Glu Lys Ile Thr Ty - #r Lys Gly Thr Trp Asp                   180      - #           185      - #           190                   - - Tyr Val Thr Asp Ala Met Glu Lys Gln Arg Ph - #e Glu Gly Leu Gly Ser               195          - #       200          - #       205                       - - Ala Ala Gly Gly Asp Lys Ser Gly Ala Leu Se - #r Ala Leu Glu Glu Gly           210              - #   215              - #   220                           - - Val Leu Arg Asn Gln Ala Glu Ala Ser Ser Gl - #y His Thr Asp Phe Gly       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Met Thr Ser Glu Phe Glu Val Asp Phe Ser As - #p Lys Thr Ile Lys         Gly                                                                                              245  - #               250  - #               255              - - Thr Leu Tyr Arg Asn Asn Arg Ile Thr Gln As - #n Asn Ser Glu Asn Lys                   260      - #           265      - #           270                   - - Gln Ile Lys Thr Thr Arg Tyr Thr Ile Gln Al - #a Thr Leu His Gly Asn               275          - #       280          - #       285                       - - Arg Phe Lys Gly Lys Ala Leu Ala Ala Asp Ly - #s Gly Ala Thr Asn Gly           290              - #   295              - #   300                           - - Ser His Pro Phe Ile Ser Asp Ser Asp Ser Le - #u Glu Gly Gly Phe Tyr       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Gly Pro Lys Gly Glu Glu Leu Ala Gly Lys Ph - #e Leu Ser Asn Asp         Asn                                                                                              325  - #               330  - #               335              - - Lys Val Ala Ala Val Phe Gly Ala Lys Gln Ly - #s Asp Lys Lys Asp Gly                   340      - #           345      - #           350                   - - Glu Asn Ala Ala Gly Pro Ala Thr Glu Val Il - #e Asp Ala Tyr Arg Ile               355          - #       360          - #       365                       - - Thr Gly Glu Glu Phe Lys Lys Glu Gln Ile As - #p Ser Phe Gly Asp Val           370              - #   375              - #   380                           - - Lys Lys Leu Leu Val Asp Gly Val Glu Leu Se - #r Leu Leu Pro Ser Glu       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Gly Asn Lys Ala Ala Phe Gln His Glu Ile Gl - #u Gln Asn Gly Val         Lys                                                                                              405  - #               410  - #               415              - - Ala Thr Val Cys Cys Ser Asn Leu Asp Tyr Me - #t Ser Phe Gly Lys Leu                   420      - #           425      - #           430                   - - Ser Lys Glu Asn Lys Asp Asp Met Phe Leu Gl - #n Gly Val Arg Thr Pro               435          - #       440          - #       445                       - - Val Ser Asp Val Ala Ala Arg Thr Glu Ala As - #n Ala Lys Tyr Arg Gly           450              - #   455              - #   460                           - - Thr Trp Tyr Gly Tyr Ile Ala Asn Gly Thr Se - #r Trp Ser Gly Glu Ala       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Ser Asn Gln Glu Gly Gly Asn Arg Ala Glu Ph - #e Asp Val Asp Phe         Ser                                                                                              485  - #               490  - #               495              - - Thr Lys Lys Ile Ser Gly Thr Leu Thr Ala Ly - #s Asp Arg Thr Ser Pro                   500      - #           505      - #           510                   - - Ala Phe Thr Ile Thr Ala Met Ile Lys Asp As - #n Gly Phe Ser Gly Val               515          - #       520          - #       525                       - - Ala Lys Thr Gly Glu Asn Gly Phe Ala Leu As - #p Pro Gln Asn Thr Gly           530              - #   535              - #   540                           - - Asn Ser His Tyr Thr His Ile Glu Ala Thr Va - #l Ser Gly Gly Phe Tyr       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Gly Lys Asn Ala Ile Glu Met Gly Gly Ser Ph - #e Ser Phe Pro Gly         Asn                                                                                              565  - #               570  - #               575              - - Ala Pro Glu Gly Lys Gln Glu Lys Ala Ser Va - #l Val Phe Gly Ala Lys                   580      - #           585      - #           590                   - - Arg Gln Gln Leu Val Gln                                                           595                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:98:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 711 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:98:                               - - Met Asn Asn Pro Leu Val Asn Gln Ala Ala Me - #t Val Leu Pro Val Phe       1               5   - #                10  - #                15                - - Leu Leu Ser Ala Cys Leu Gly Gly Gly Gly Se - #r Phe Asp Leu Asp Ser                   20      - #            25      - #            30                    - - Val Asp Thr Glu Ala Pro Arg Pro Ala Pro Ly - #s Tyr Gln Asp Val Ser               35          - #        40          - #        45                        - - Ser Glu Lys Pro Gln Ala Gln Lys Asp Gln Gl - #y Gly Tyr Gly Phe Ala           50              - #    55              - #    60                            - - Met Arg Leu Lys Arg Arg Asn Trp Tyr Pro Gl - #y Ala Glu Glu Ser Glu       65                  - #70                  - #75                  - #80         - - Val Lys Leu Asn Glu Ser Asp Trp Glu Ala Th - #r Gly Leu Pro Thr Lys                       85  - #                90  - #                95                - - Pro Lys Glu Leu Pro Lys Arg Gln Lys Ser Va - #l Ile Glu Lys Val Glu                   100      - #           105      - #           110                   - - Thr Asp Gly Asp Ser Asp Ile Tyr Ser Ser Pr - #o Tyr Leu Thr Pro Ser               115          - #       120          - #       125                       - - Asn His Gln Asn Gly Ser Ala Gly Asn Gly Va - #l Asn Gln Pro Lys Asn           130              - #   135              - #   140                           - - Gln Ala Thr Gly His Glu Asn Phe Gln Tyr Va - #l Tyr Ser Gly Trp Phe       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Tyr Lys His Ala Ala Ser Glu Lys Asp Phe Se - #r Asn Lys Lys Ile         Lys                                                                                              165  - #               170  - #               175              - - Ser Gly Asp Asp Gly Tyr Ile Phe Tyr His Gl - #y Glu Lys Pro Ser Arg                   180      - #           185      - #           190                   - - Gln Leu Pro Ala Ser Gly Lys Val Ile Tyr Ly - #s Gly Val Trp His Phe               195          - #       200          - #       205                       - - Val Thr Asp Thr Lys Lys Gly Gln Asp Phe Ar - #g Glu Ile Ile Gln Pro           210              - #   215              - #   220                           - - Ser Lys Lys Gln Gly Asp Arg Tyr Ser Gly Ph - #e Ser Gly Asp Gly Ser       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Glu Glu Tyr Ser Asn Lys Asn Glu Ser Thr Le - #u Lys Asp Asp His         Glu                                                                                              245  - #               250  - #               255              - - Gly Tyr Gly Phe Thr Ser Asn Leu Glu Val As - #p Phe Gly Asn Lys Lys                   260      - #           265      - #           270                   - - Leu Thr Gly Lys Leu Ile Arg Asn Asn Ala Se - #r Leu Asn Asn Asn Thr               275          - #       280          - #       285                       - - Asn Asn Asp Lys His Thr Thr Gln Tyr Tyr Se - #r Leu Asp Ala Gln Ile           290              - #   295              - #   300                           - - Thr Gly Asn Arg Phe Asn Gly Thr Ala Thr Al - #a Thr Asp Lys Lys Glu       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Asn Glu Thr Lys Leu His Pro Phe Val Ser As - #p Ser Ser Ser Leu         Ser                                                                                              325  - #               330  - #               335              - - Gly Gly Phe Phe Gly Pro Gln Gly Glu Glu Le - #u Gly Phe Arg Phe Leu                   340      - #           345      - #           350                   - - Ser Asp Asp Gln Lys Val Ala Val Val Gly Se - #r Ala Lys Thr Lys Asp               355          - #       360          - #       365                       - - Lys Leu Glu Asn Gly Ala Ala Ala Ser Gly Se - #r Thr Gly Ala Ala Ala           370              - #   375              - #   380                           - - Ser Gly Gly Ala Ala Gly Thr Ser Ser Glu As - #n Ser Lys Leu Thr Thr       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Val Leu Asp Ala Val Glu Leu Thr Leu Asn As - #p Lys Lys Ile Lys         Asn                                                                                              405  - #               410  - #               415              - - Leu Asp Asn Phe Ser Asn Ala Ala Gln Leu Va - #l Val Asp Gly Ile Met                   420      - #           425      - #           430                   - - Ile Pro Leu Leu Pro Lys Asp Ser Glu Ser Gl - #y Asn Thr Gln Ala Asp               435          - #       440          - #       445                       - - Lys Gly Lys Asn Gly Gly Thr Glu Phe Thr Ar - #g Lys Phe Glu His Thr           450              - #   455              - #   460                           - - Pro Glu Ser Asp Lys Lys Asp Ala Gln Ala Gl - #y Thr Gln Thr Asn Gly       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Ala Gln Thr Ala Ser Asn Thr Ala Gly Asp Th - #r Asn Gly Lys Thr         Lys                                                                                              485  - #               490  - #               495              - - Thr Tyr Glu Val Glu Val Cys Cys Ser Asn Le - #u Asn Tyr Leu Lys Tyr                   500      - #           505      - #           510                   - - Gly Met Leu Thr Arg Lys Asn Ser Lys Ser Al - #a Met Gln Ala Gly Gly               515          - #       520          - #       525                       - - Asn Ser Ser Gln Ala Asp Ala Lys Thr Glu Gl - #n Val Glu Gln Ser Met           530              - #   535              - #   540                           - - Phe Leu Gln Gly Glu Arg Thr Asp Glu Lys Gl - #u Ile Pro Thr Asp Gln       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Asn Val Val Tyr Arg Gly Ser Trp Tyr Gly Hi - #s Ile Ala Asn Gly         Thr                                                                                              565  - #               570  - #               575              - - Ser Trp Ser Gly Asn Ala Ser Asp Lys Glu Gl - #y Gly Asn Arg Ala Glu                   580      - #           585      - #           590                   - - Phe Thr Val Asn Phe Ala Asp Lys Lys Ile Th - #r Gly Lys Leu Thr Ala               595          - #       600          - #       605                       - - Glu Asn Arg Gln Ala Gln Thr Phe Thr Ile Gl - #u Gly Met Ile Gln Gly           610              - #   615              - #   620                           - - Asn Gly Phe Glu Gly Thr Ala Lys Thr Ala Gl - #u Ser Gly Phe Asp Leu       625                 6 - #30                 6 - #35                 6 -       #40                                                                               - - Asp Gln Lys Asn Thr Thr Arg Thr Pro Lys Al - #a Tyr Ile Thr Asp         Ala                                                                                              645  - #               650  - #               655              - - Lys Val Lys Gly Gly Phe Tyr Gly Pro Lys Al - #a Glu Glu Leu Gly Gly                   660      - #           665      - #           670                   - - Trp Phe Ala Tyr Pro Gly Asp Lys Gln Thr Gl - #u Lys Ala Thr Ala Thr               675          - #       680          - #       685                       - - Ser Ser Asp Gly Asn Ser Ala Ser Ser Ala Th - #r Val Val Phe Gly Ala           690              - #   695              - #   700                           - - Lys Arg Gln Gln Pro Val Gln                                               705                 7 - #10                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:99:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 546 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:99:                               - - Met His Phe Lys Leu Asn Pro Tyr Ala Leu Al - #a Phe Thr Ser Leu Phe       1               5   - #                10  - #                15                - - Leu Val Ala Cys Ser Gly Gly Lys Gly Ser Ph - #e Asp Leu Glu Asp Val                   20      - #            25      - #            30                    - - Arg Pro Asn Lys Thr Thr Gly Val Ser Lys Gl - #u Glu Tyr Lys Asp Val               35          - #        40          - #        45                        - - Glu Thr Ala Lys Lys Glu Lys Glu Gln Leu Gl - #y Glu Leu Met Glu Pro           50              - #    55              - #    60                            - - Ala Leu Gly Tyr Val Val Lys Val Pro Val Se - #r Ser Phe Glu Asn Lys       65                  - #70                  - #75                  - #80         - - Lys Val Asp Ile Ser Asp Ile Glu Val Ile Th - #r Asn Gly Asn Leu Asp                       85  - #                90  - #                95                - - Asp Val Pro Tyr Lys Ala Asn Ser Ser Lys Ty - #r Asn Tyr Pro Asp Ile                   100      - #           105      - #           110                   - - Lys Thr Lys Asp Ser Ser Leu Gln Tyr Val Ar - #g Ser Gly Tyr Val Ile               115          - #       120          - #       125                       - - Asp Gly Glu His Ser Gly Ser Asn Glu Lys Gl - #y Tyr Val Tyr Tyr Lys           130              - #   135              - #   140                           - - Gly Asn Ser Pro Ala Lys Glu Leu Pro Val As - #n Gln Leu Leu Thr Tyr       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Thr Gly Ser Trp Asp Phe Thr Ser Asn Ala As - #n Leu Asn Asn Glu         Glu                                                                                              165  - #               170  - #               175              - - Gly Arg Pro Asn Tyr Leu Asn Asp Asp Tyr Ty - #r Thr Lys Phe Ile Gly                   180      - #           185      - #           190                   - - Lys Arg Val Gly Leu Val Ser Gly Asp Ala Ly - #s Pro Ala Lys His Lys               195          - #       200          - #       205                       - - Tyr Thr Ser Gln Phe Glu Val Asp Phe Ala Th - #r Lys Lys Met Thr Gly           210              - #   215              - #   220                           - - Lys Ser Asp Lys Glu Lys Thr Ile Tyr Thr Va - #l Asn Ala Asp Ile Arg       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Gly Asn Arg Phe Thr Gly Ala Ala Thr Ala Se - #r Asp Lys Asn Lys         Gly                                                                                              245  - #               250  - #               255              - - Lys Gly Glu Ser Tyr Asn Phe Phe Ser Ala As - #p Ser Gln Ser Leu Glu                   260      - #           265      - #           270                   - - Gly Gly Phe Tyr Gly Pro Lys Ala Glu Glu Me - #t Ala Gly Lys Phe Val               275          - #       280          - #       285                       - - Ala Asn Asp Lys Ser Leu Phe Ala Val Phe Se - #r Ala Lys His Asn Gly           290              - #   295              - #   300                           - - Ser Asn Val Asn Thr Val Arg Ile Ile Asp Al - #a Ser Lys Ile Asp Leu       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Thr Asn Phe Ser Ile Ser Glu Leu Asn Asn Ph - #e Gly Asp Ala Ser         Val                                                                                              325  - #               330  - #               335              - - Leu Ile Ile Asp Gly Lys Lys Ile Lys Leu Al - #a Gly Ser Gly Phe Thr                   340      - #           345      - #           350                   - - Asn Lys His Thr Ile Glu Ile Asn Gly Lys Th - #r Met Val Ala Val Ala               355          - #       360          - #       365                       - - Cys Cys Ser Asn Leu Glu Tyr Met Lys Phe Gl - #y Gln Leu Trp Gln Gln           370              - #   375              - #   380                           - - Ala Glu Gly Gly Lys Pro Glu Asn Asn Ser Le - #u Phe Leu Gln Gly Glu       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Arg Thr Ala Thr Asp Lys Met Pro Lys Gly Gl - #y Asn Tyr Lys Tyr         Ile                                                                                              405  - #               410  - #               415              - - Gly Thr Trp Asp Ala Gln Val Ser Lys Glu As - #n Asn Trp Val Ala Thr                   420      - #           425      - #           430                   - - Ala Asp Asp Asp Arg Lys Ala Gly Tyr Arg Th - #r Glu Phe Asp Val Asp               435          - #       440          - #       445                       - - Phe Gly Asn Lys Asn Leu Ser Gly Lys Leu Ph - #e Asp Lys Asn Gly Val           450              - #   455              - #   460                           - - Asn Pro Val Phe Thr Val Asp Ala Lys Ile As - #p Gly Asn Gly Phe Thr       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Gly Lys Ala Lys Thr Ser Asp Glu Gly Phe Al - #a Leu Asp Ser Gly         Ser                                                                                              485  - #               490  - #               495              - - Ser Arg Tyr Glu Asn Val Lys Phe Asn Asp Va - #l Ala Val Ser Gly Gly                   500      - #           505      - #           510                   - - Phe Tyr Gly Pro Thr Ala Ala Glu Leu Gly Gl - #y Gln Phe His His Lys               515          - #       520          - #       525                       - - Ser Glu Asn Gly Ser Val Gly Ala Val Phe Gl - #y Ala Lys Gln Gln Val           530              - #   535              - #   540                           - - Lys Lys                                                                   545                                                                             - -  - - (2) INFORMATION FOR SEQ ID NO:100:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 593 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:100:                              - - Met His Phe Lys Leu Asn Pro Tyr Ala Leu Al - #a Phe Thr Ser Leu Phe       1               5   - #                10  - #                15                - - Leu Val Ala Cys Ser Gly Gly Lys Gly Ser Ph - #e Asp Leu Glu Asp Val                   20      - #            25      - #            30                    - - Arg Pro Asn Gln Thr Ala Lys Ala Glu Lys Al - #a Thr Thr Ser Tyr Gln               35          - #        40          - #        45                        - - Asp Glu Glu Thr Lys Lys Lys Thr Lys Glu Gl - #u Leu Asp Lys Leu Met           50              - #    55              - #    60                            - - Glu Pro Ala Leu Gly Tyr Glu Thr Gln Ile Le - #u Arg Arg Asn Lys Ala       65                  - #70                  - #75                  - #80         - - Pro Lys Thr Glu Thr Gly Glu Lys Arg Asn Gl - #u Arg Val Val Glu Leu                       85  - #                90  - #                95                - - Ser Glu Asp Lys Ile Thr Lys Leu Tyr Gln Gl - #u Ser Val Glu Ile Ile                   100      - #           105      - #           110                   - - Pro His Leu Asp Glu Leu Asn Gly Lys Thr Th - #r Ser Asn Asp Val Tyr               115          - #       120          - #       125                       - - His Ser His Asp Ser Lys Arg Leu Asp Lys As - #n Arg Asp Leu Lys Tyr           130              - #   135              - #   140                           - - Val Arg Ser Gly Tyr Val Tyr Asp Gly Ser Ph - #e Asn Glu Ile Arg Arg       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Asn Asp Ser Gly Phe His Val Phe Lys Gln Gl - #y Ile Asp Gly Tyr         Val                                                                                              165  - #               170  - #               175              - - Tyr Tyr Leu Gly Val Thr Pro Ser Lys Glu Le - #u Pro Lys Gly Lys Val                   180      - #           185      - #           190                   - - Ile Ser Tyr Lys Gly Thr Trp Asp Phe Val Se - #r Asn Ile Asn Leu Glu               195          - #       200          - #       205                       - - Arg Glu Ile Asp Gly Phe Asp Thr Ser Gly As - #p Gly Lys Asn Val Ser           210              - #   215              - #   220                           - - Ala Thr Ser Ile Thr Glu Thr Val Asn Arg As - #p His Lys Val Gly Glu       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Lys Leu Gly Asp Asn Glu Val Lys Gly Val Al - #a His Ser Ser Glu         Phe                                                                                              245  - #               250  - #               255              - - Ala Val Asp Phe Asp Asn Lys Lys Leu Thr Gl - #y Ser Leu Tyr Arg Asn                   260      - #           265      - #           270                   - - Gly Tyr Ile Asn Arg Asn Lys Ala Gln Glu Va - #l Thr Lys Arg Tyr Ser               275          - #       280          - #       285                       - - Ile Glu Ala Asp Ile Ala Gly Asn Arg Phe Ar - #g Gly Lys Ala Lys Ala           290              - #   295              - #   300                           - - Glu Lys Ala Gly Asp Pro Ile Phe Thr Asp Se - #r Asn Tyr Leu Glu Gly       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Gly Phe Tyr Gly Pro Lys Ala Glu Glu Met Al - #a Gly Lys Phe Phe         Thr                                                                                              325  - #               330  - #               335              - - Asn Asn Lys Ser Leu Phe Ala Val Phe Ala Al - #a Lys Ser Glu Asn Gly                   340      - #           345      - #           350                   - - Glu Thr Thr Thr Glu Arg Ile Ile Asp Ala Th - #r Lys Ile Asp Leu Thr               355          - #       360          - #       365                       - - Gln Phe Asn Ala Lys Glu Leu Asn Asn Phe Gl - #y Asp Ala Ser Val Leu           370              - #   375              - #   380                           - - Ile Ile Asp Gly Gln Lys Ile Asp Leu Ala Gl - #y Val Asn Phe Lys Asn       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Ser Lys Thr Val Glu Ile Asn Gly Lys Thr Me - #t Val Ala Val Ala         Cys                                                                                              405  - #               410  - #               415              - - Cys Ser Asn Leu Glu Tyr Met Lys Phe Gly Gl - #n Leu Trp Gln Lys Glu                   420      - #           425      - #           430                   - - Gly Lys Gln Gln Val Lys Asp Asn Ser Leu Ph - #e Leu Gln Gly Glu Arg               435          - #       440          - #       445                       - - Thr Ala Thr Asp Lys Met Pro Ala Gly Gly As - #n Tyr Lys Tyr Val Gly           450              - #   455              - #   460                           - - Thr Trp Asp Ala Leu Val Ser Lys Gly Thr As - #n Trp Ile Ala Glu Ala       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Asp Asn Asn Arg Glu Ser Gly Tyr Arg Thr Gl - #u Phe Asp Val Asn         Phe                                                                                              485  - #               490  - #               495              - - Ser Asp Lys Lys Val Asn Gly Lys Leu Phe As - #p Lys Gly Gly Val Asn                   500      - #           505      - #           510                   - - Pro Val Phe Thr Val Asp Ala Thr Ile Asn Gl - #y Asn Gly Phe Ile Gly               515          - #       520          - #       525                       - - Ser Ala Lys Thr Ser Asp Ser Gly Phe Ala Le - #u Asp Ala Gly Ser Ser           530              - #   535              - #   540                           - - Gln His Gly Asn Ala Val Phe Ser Asp Ile Ly - #s Val Asn Gly Gly Phe       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Tyr Gly Pro Thr Ala Gly Glu Leu Gly Gly Gl - #n Phe His His Lys         Ser                                                                                              565  - #               570  - #               575              - - Asp Asn Gly Ser Val Gly Ala Val Phe Gly Al - #a Lys Arg Gln Ile Glu                   580      - #           585      - #           590                   - - Lys                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:101:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 18 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:101:                              - - Glu Thr Gln Ser Ile Lys Asp Thr Lys Glu Al - #a Ile Ser Ser Glu Val       1               5   - #                10  - #                15                - - Asp Thr                                                                    - -  - - (2) INFORMATION FOR SEQ ID NO:102:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 20 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:102:                              - - Leu Gln Leu Asn Leu Glu Lys Lys Ile Gln Gl - #n Asn Trp Leu Thr His       1               5   - #                10  - #                15                - - Gln Ile Ala Phe                                                                       20                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:103:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 23 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:103:                              - - Met Thr Lys Lys Pro Tyr Phe Arg Leu Ser Il - #e Ile Ser Cys Leu Leu       1               5   - #                10  - #                15                - - Ile Ser Cys Tyr Val Lys Ala                                                           20                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:104:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 17 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO:104:                              - - Met Lys Ser Val Pro Leu Ile Ser Gly Gly Le - #u Ser Phe Leu Leu Ser       1               5   - #                10  - #                15                - - Ala                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO: 105:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 5144 base - #pairs                                                 (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ix) FEATURE:                                                                   (A) NAME/KEY: CDS                                                              (B) LOCATION: join(192..69 - #5, 2135..4867)                          - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #105:                          - - CAACATCTGC CCAAGCTATA TTCGTTAATG ATAAGCCTAT TAATGATAAG CC -              #TATTAATG     60                                                                  - - ATAAGAAAGA AATTTGTTTT ACGCCATTTT TCATATTTTA TCCATGAACT TA -             #AAAAATTC    120                                                                  - - TAAGTTGACA TTATTACAAA AAAAGAACAA TAATGCGAAT TATTATCAAT TT -             #TGTATAAG    180                                                                  - - AATATAATTC T ATG AAA TCT GTA CCT CTT ATC TCT - #GGT GGA CTT TCC         TTT     230                                                                                   Met Lys Ser - #Val Pro Leu Ile Ser Gly Gly Leu Ser Phe                          1   - #            5      - #            10                      - - TTA TTA AGT GCT TGT AGC GGA GGA GGG TCT TT - #T GAT GTA GAT AAC GTC           278                                                                        Leu Leu Ser Ala Cys Ser Gly Gly Gly Ser Ph - #e Asp Val Asp Asn Val                 15             - #     20             - #     25                           - - TCT AAT CCC TCC TCT TCT AAA CCA CGT TAT CA - #A GAC GAT ACC TCG AAT           326                                                                        Ser Asn Pro Ser Ser Ser Lys Pro Arg Tyr Gl - #n Asp Asp Thr Ser Asn             30                 - # 35                 - # 40                 - # 45        - - CAA AGA ACA AAA TCT GAT TTG CAA AAG TTG TC - #C ATT CCT TCT TTA GGG           374                                                                        Gln Arg Thr Lys Ser Asp Leu Gln Lys Leu Se - #r Ile Pro Ser Leu Gly                             50 - #                 55 - #                 60               - - GGA GGG ATG AAG TTA GTG GCT CAG AAT CTT CT - #T GGT AAG AAA GAA CCT           422                                                                        Gly Gly Met Lys Leu Val Ala Gln Asn Leu Le - #u Gly Lys Lys Glu Pro                         65     - #             70     - #             75                   - - AGT CTC TTA AAT AAT GAA GAT GGC TAT ATG AT - #A TTT TCC TCA CTT TCT           470                                                                        Ser Leu Leu Asn Asn Glu Asp Gly Tyr Met Il - #e Phe Ser Ser Leu Ser                     80         - #         85         - #         90                       - - ACG ATT GAA GAG GAT GTT ACA AAA GAA AAT AA - #A TCT CAG GAA CCC ACT           518                                                                        Thr Ile Glu Glu Asp Val Thr Lys Glu Asn Ly - #s Ser Gln Glu Pro Thr                 95             - #    100             - #    105                           - - ATT GGC TCA ATA GAC GAG CCT AGC AAA ACA AA - #T TCA CCC CAA AAT CAT           566                                                                        Ile Gly Ser Ile Asp Glu Pro Ser Lys Thr As - #n Ser Pro Gln Asn His            110                 1 - #15                 1 - #20                 1 -       #25                                                                               - - CAT GGC AAT ATG TAT ATT CGG GTC TTT ATT AT - #A TTC AAT CGT GGC         GTA      614                                                                     His Gly Asn Met Tyr Ile Arg Val Phe Ile Il - #e Phe Asn Arg Gly Val                           130  - #               135  - #               140               - - ATT CCT CAA ATG GCA AGT TTT ATT CAG GTT AC - #T ATG GAT ATG CGT ATT           662                                                                        Ile Pro Gln Met Ala Ser Phe Ile Gln Val Th - #r Met Asp Met Arg Ile                        145      - #           150      - #           155                   - - ACT TTG GCA AGC AAA CAG CCA CTA CAT TAC CT - #G TAGATGGCGA AGCAACGTA     T    715                                                                        Thr Leu Ala Ser Lys Gln Pro Leu His Tyr Le - #u                                        160          - #       165                                              - - AAAGGAACTT GGCACTTCAT CACCGCAACT GAAAATGGCA AAAAGTATTC TT -              #TGTTCAGT    775                                                                  - - AATGATAGCG GTCAAGCTTA TCGCAGACGT AGTGCAATTC CAGAAGATAT TG -             #ATTTAGAA    835                                                                  - - AAAAATGATT CAACTAATGG TGACAAGGGC TTAATAAGTG AATTTAGTGT CA -             #ATTTTGGT    895                                                                  - - ACAAAAAAGC TCACTGGAAA ACTTTATTAT AATGAAAGAG AAACAGAACT TA -             #ATAAATCA    955                                                                  - - AAAGATAGAA AACATACACT CTACAATCTA GAAGCTGAAG TGTATAGTAA CC -             #GATTCAGG   1015                                                                  - - GGTACAGTAA AGCCAACCGA AAAAGATTCT ACAGATCATC CCTTTACCAG CG -             #AGGGAACA   1075                                                                  - - TTAGAAGGTG GTTTTTATGG GCCTAAAGGT GAAGAACTAG GAGGAAAGTT TT -             #TAGCTGGC   1135                                                                  - - GATAAAAAAG TTTTTGGGGT ATTTAGTGCC AAAGAAACGG AAGAAACAAA AA -             #AGAAAGCG   1195                                                                  - - TTATCCAAGG AAACCTTAAT TGATGGCAAG CTAACTACTT TTAAAACAAC CA -             #ATGCAACA   1255                                                                  - - ACCAATGCAA CAGCCAATGC AACAACCAGT ACAACAGCCA GTACAACAAC CG -             #ATGCAGAA   1315                                                                  - - AACTTTACGA CGAAAGATAT ACCAAGTTTT GGTGAAGCTG ATTACCTTTT AA -             #TTGATAAT   1375                                                                  - - TACCCTGTTC CTCTTTTACC TGAGAGTGGT GATTTCATAA GTAGTAAGCA CC -             #ATACTGTA   1435                                                                  - - GGAAAGAAAA CCTATCAAGT AGAAGCATGT TGCAGTAATC TAAGCTATGT GA -             #AATTTGGT   1495                                                                  - - ATGTTTTATG AAGACCCACT TAAAGAAGAA AAAGACAAAG AAAAAGAAGA AG -             #ACAAAGAA   1555                                                                  - - AAACAAACGG CGGCAACGAC CAACACTTAT TATCAATTCT TATTAGGTCT CC -             #GTACTGCC   1615                                                                  - - AGTTCTGAAA TTCCTAAAAT GGGAAACGTG GAATATCGCG GTAATTGGTT TG -             #GTTATATT   1675                                                                  - - AGTGATGGCA CGACATCTTA CTCCCCCAGT GGTGATAAGG AACGCAATAA AA -             #ATGCTCCC   1735                                                                  - - GCCGATTTTA ATGTTGATTT TGTCAATAAA AAGCTAACAG GCACATTAAA AC -             #GACACGAT   1795                                                                  - - AATGGAAATA CCGTATTTAG TATTGAGGCA AACTTTAACA GTGGGAATGA CT -             #TCACTGGT   1855                                                                  - - AAAGCAACCG CAAAAGATTT AGTAATAGAT GGTAAAAGTA CACAAGCCAC AT -             #CTAAAGTC   1915                                                                  - - AATTTCACGG CAACAGTAAA AGGGGCATTT TATGGACCTG ATGCTTCTGA AT -             #TAGGCGGT   1975                                                                  - - TATTTCACCT ATAACGGAAA AAATCCTACA GCTACAAATT CCCCAACCGT AT -             #CTTCACCA   2035                                                                  - - TCCAATTCAG CAAATGCTCG TGCTGCCGTT GTGTTTGGAG CTAAAAAACA AG -             #TAGACACA   2095                                                                  - - ACCAACAAGT AGAAAAAACC AAATAATGGA ATACTAAAA ATG ACT AAA - # AAA CCC           2149                                                                                         - #                  - #       Met Thr Lys Lys Pro                             - #                  - #           170                        - - TAT TTT CGC CTA AGT ATT ATT TCT TGT CTT TT - #A ATT TCA TGC TAT GTA          2197                                                                        Tyr Phe Arg Leu Ser Ile Ile Ser Cys Leu Le - #u Ile Ser Cys Tyr Val                175              - #   180              - #   185                           - - AAA GCA GAA ACT CAA AGT ATA AAA GAT ACA AA - #A GAA GCT ATA TCA TCT          2245                                                                        Lys Ala Glu Thr Gln Ser Ile Lys Asp Thr Ly - #s Glu Ala Ile Ser Ser            190                 1 - #95                 2 - #00                 2 -       #05                                                                               - - GAA GTG GAC ACT CAA AGT ACA GAA GAT TCA GA - #A TTA GAA ACT ATC         TCA     2293                                                                     Glu Val Asp Thr Gln Ser Thr Glu Asp Ser Gl - #u Leu Glu Thr Ile Ser                           210  - #               215  - #               220               - - GTC ACT GCA GAA AAA ATA AGA GAT CGT AAA GA - #T AAT GAA GTA ACT GGA          2341                                                                        Val Thr Ala Glu Lys Ile Arg Asp Arg Lys As - #p Asn Glu Val Thr Gly                        225      - #           230      - #           235                   - - CTT GGC AAA ATT ATA AAA ACG AGT GAA AGT AT - #C AGC CGA GAA CAA GTA          2389                                                                        Leu Gly Lys Ile Ile Lys Thr Ser Glu Ser Il - #e Ser Arg Glu Gln Val                    240          - #       245          - #       250                       - - TTA AAT ATT CGT GAT CTA ACA CGC TAT GAT CC - #A GGC ATT TCA GTT GTA          2437                                                                        Leu Asn Ile Arg Asp Leu Thr Arg Tyr Asp Pr - #o Gly Ile Ser Val Val                255              - #   260              - #   265                           - - GAA CAA GGT CGC GGT GCA AGT TCT GGA TAT TC - #T ATT CGT GGT ATG GAC          2485                                                                        Glu Gln Gly Arg Gly Ala Ser Ser Gly Tyr Se - #r Ile Arg Gly Met Asp            270                 2 - #75                 2 - #80                 2 -       #85                                                                               - - AGA AAT AGA GTT GCT TTA TTA GTA GAT GGT TT - #A CCT CAA ACG CAA         TCT     2533                                                                     Arg Asn Arg Val Ala Leu Leu Val Asp Gly Le - #u Pro Gln Thr Gln Ser                           290  - #               295  - #               300               - - TAT GTA GTG CAA AGC CCT TTA GTT GCT CGT TC - #A GGA TAT TCT GGC ACT          2581                                                                        Tyr Val Val Gln Ser Pro Leu Val Ala Arg Se - #r Gly Tyr Ser Gly Thr                        305      - #           310      - #           315                   - - GGT GCA ATT AAT GAA ATT GAA TAT GAA AAT GT - #A AAG GCC GTC GAA ATA          2629                                                                        Gly Ala Ile Asn Glu Ile Glu Tyr Glu Asn Va - #l Lys Ala Val Glu Ile                    320          - #       325          - #       330                       - - AGC AAG GGG GGG AGT TCT TCT GAG TAT GGT AA - #T GGA GCA CTA GCT GGT          2677                                                                        Ser Lys Gly Gly Ser Ser Ser Glu Tyr Gly As - #n Gly Ala Leu Ala Gly                335              - #   340              - #   345                           - - TCT GTA ACA TTT CAA AGC AAA TCC GCA GCC GA - #T ATC TTA GAA GGA GAC          2725                                                                        Ser Val Thr Phe Gln Ser Lys Ser Ala Ala As - #p Ile Leu Glu Gly Asp            350                 3 - #55                 3 - #60                 3 -       #65                                                                               - - AAA TCA TGG GGA ATT CAA ACT AAA AAT GCT TA - #T TCA AGC AAA AAT         AAA     2773                                                                     Lys Ser Trp Gly Ile Gln Thr Lys Asn Ala Ty - #r Ser Ser Lys Asn Lys                           370  - #               375  - #               380               - - GGC TTT ACC CAT TCT TTA GCT GTA GCA GGA AA - #A CAA GGT GGA TTT GAA          2821                                                                        Gly Phe Thr His Ser Leu Ala Val Ala Gly Ly - #s Gln Gly Gly Phe Glu                        385      - #           390      - #           395                   - - GGG GTC GCC ATT TAC ACT CAA CGA AAT TCG GA - #G GAA ACC CAA GTC CAT          2869                                                                        Gly Val Ala Ile Tyr Thr Gln Arg Asn Ser Gl - #u Glu Thr Gln Val His                    400          - #       405          - #       410                       - - AAA GAT GCA TTA AAA GGC GTA CAA AGT TAT GA - #G CGA TTC ATC GCC ACA          2917                                                                        Lys Asp Ala Leu Lys Gly Val Gln Ser Tyr Gl - #u Arg Phe Ile Ala Thr                415              - #   420              - #   425                           - - ACA GAT AAA TCT TCA GGA TAC TTT GTG ATA CA - #A GGT GAG TGT CCA AAT          2965                                                                        Thr Asp Lys Ser Ser Gly Tyr Phe Val Ile Gl - #n Gly Glu Cys Pro Asn            430                 4 - #35                 4 - #40                 4 -       #45                                                                               - - GGT GAT GAC AAG TGT GCA GCC AAA CCA CCT GC - #A AAG TTA TCC CCC         CAA     3013                                                                     Gly Asp Asp Lys Cys Ala Ala Lys Pro Pro Al - #a Lys Leu Ser Pro Gln                           450  - #               455  - #               460               - - AGC GAA ACC GTA AGC GTT TCA GAT TAT ACG GG - #G GCT AAC CGT ATC AAA          3061                                                                        Ser Glu Thr Val Ser Val Ser Asp Tyr Thr Gl - #y Ala Asn Arg Ile Lys                        465      - #           470      - #           475                   - - CCT AAT CCA ATG AAA TAT GAA AGC CAG TCT TG - #G TTT TTA AGA GGA GGG          3109                                                                        Pro Asn Pro Met Lys Tyr Glu Ser Gln Ser Tr - #p Phe Leu Arg Gly Gly                    480          - #       485          - #       490                       - - TAT CAT TTT TCT GAA CAA CAC TAT ATT GGT GG - #T ATT TTT GAA TTC ACA          3157                                                                        Tyr His Phe Ser Glu Gln His Tyr Ile Gly Gl - #y Ile Phe Glu Phe Thr                495              - #   500              - #   505                           - - CAA CAA AAA TTT GAT ATC CGT GAT ATG ACA TT - #T CCC GCT TAT TTA AGA          3205                                                                        Gln Gln Lys Phe Asp Ile Arg Asp Met Thr Ph - #e Pro Ala Tyr Leu Arg            510                 5 - #15                 5 - #20                 5 -       #25                                                                               - - TCA ACA GAA AAA CGG GAT GAT AGA ACT GGC CC - #T TTT TAT CCA AAG         CAA     3253                                                                     Ser Thr Glu Lys Arg Asp Asp Arg Thr Gly Pr - #o Phe Tyr Pro Lys Gln                           530  - #               535  - #               540               - - GAT TAT GGT GCA TAT CAA CGT ATT GAG GAT GG - #C CGA GGC GTT AAC TAT          3301                                                                        Asp Tyr Gly Ala Tyr Gln Arg Ile Glu Asp Gl - #y Arg Gly Val Asn Tyr                        545      - #           550      - #           555                   - - GCA AGT GGG CTT TAT TTC GAT GAA CAC CAT AG - #A AAA CAG CGT GTA GGT          3349                                                                        Ala Ser Gly Leu Tyr Phe Asp Glu His His Ar - #g Lys Gln Arg Val Gly                    560          - #       565          - #       570                       - - ATT GAA TAT ATT TAC GAA AAT AAG AAC AAA GC - #G GGC ATC ATT GAC AAA          3397                                                                        Ile Glu Tyr Ile Tyr Glu Asn Lys Asn Lys Al - #a Gly Ile Ile Asp Lys                575              - #   580              - #   585                           - - GCA GTG TTA AGT GCT AAT CAA CAA AAC ATC AT - #A CTT GAC AGT TAT ATG          3445                                                                        Ala Val Leu Ser Ala Asn Gln Gln Asn Ile Il - #e Leu Asp Ser Tyr Met            590                 5 - #95                 6 - #00                 6 -       #05                                                                               - - CGA CAT ACG CAT TGC AGT CTT TAT CCT AAT CC - #A AGT AAG AAT TGC         CGC     3493                                                                     Arg His Thr His Cys Ser Leu Tyr Pro Asn Pr - #o Ser Lys Asn Cys Arg                           610  - #               615  - #               620               - - CCG ACA CTT GAT AAA CCT TAT TCA TAC TAT CG - #T TCT GAT AGA AAT GTT          3541                                                                        Pro Thr Leu Asp Lys Pro Tyr Ser Tyr Tyr Ar - #g Ser Asp Arg Asn Val                        625      - #           630      - #           635                   - - TAT AAA GAA AAA CAT AAT ATG TTG CAA TTG AA - #T TTA GAG AAA AAA ATT          3589                                                                        Tyr Lys Glu Lys His Asn Met Leu Gln Leu As - #n Leu Glu Lys Lys Ile                    640          - #       645          - #       650                       - - CAA CAA AAT TGG CTT ACT CAT CAA ATT GTC TT - #C AAT CTT GGT TTT GAT          3637                                                                        Gln Gln Asn Trp Leu Thr His Gln Ile Val Ph - #e Asn Leu Gly Phe Asp                655              - #   660              - #   665                           - - GAC TTT ACT TCA GCG CTT CAG CAT AAA GAT TA - #T TTA ACT CGA CGT GTT          3685                                                                        Asp Phe Thr Ser Ala Leu Gln His Lys Asp Ty - #r Leu Thr Arg Arg Val            670                 6 - #75                 6 - #80                 6 -       #85                                                                               - - ACC GCT ACG GCA AAT ATT ATT TCA GGG ACA GT - #T GCT GGT AAA CGA         AGA     3733                                                                     Thr Ala Thr Ala Asn Ile Ile Ser Gly Thr Va - #l Ala Gly Lys Arg Arg                           690  - #               695  - #               700               - - AAT GGT TAC GAA AAA CAA CCT TAC TTA TAC TC - #A AAA CCA AAA GTA GAT          3781                                                                        Asn Gly Tyr Glu Lys Gln Pro Tyr Leu Tyr Se - #r Lys Pro Lys Val Asp                        705      - #           710      - #           715                   - - TTT GTA GGA CAA GAT CAT TGT AAT TAT AAA GG - #T AGC TCC TCT AAT TAC          3829                                                                        Phe Val Gly Gln Asp His Cys Asn Tyr Lys Gl - #y Ser Ser Ser Asn Tyr                    720          - #       725          - #       730                       - - AGC GAC TGT AAA GTG CGG TTA ATT AAA GGG AA - #A AAT TAT TAT TTC GCA          3877                                                                        Ser Asp Cys Lys Val Arg Leu Ile Lys Gly Ly - #s Asn Tyr Tyr Phe Ala                735              - #   740              - #   745                           - - GCA CGC AAT AAT ATG GCA TTA GGG AAA TAC AT - #T GAT TTA GGT TTA GGT          3925                                                                        Ala Arg Asn Asn Met Ala Leu Gly Lys Tyr Il - #e Asp Leu Gly Leu Gly            750                 7 - #55                 7 - #60                 7 -       #65                                                                               - - ATT CGG TAT GAC GTA TCT CGT ACA AAA GCT AA - #T GAA TCA ACT ATT         AGT     3973                                                                     Ile Arg Tyr Asp Val Ser Arg Thr Lys Ala As - #n Glu Ser Thr Ile Ser                           770  - #               775  - #               780               - - GTT GGT AAA TTT AAA AAT TTC TCT TGG AAT AC - #T GGT ATT GTC ATA AAA          4021                                                                        Val Gly Lys Phe Lys Asn Phe Ser Trp Asn Th - #r Gly Ile Val Ile Lys                        785      - #           790      - #           795                   - - CCA ACG GAA TGG CTT GAT CTT TCT TAT CGC CT - #T TCT ACT GGA TTT AGA          4069                                                                        Pro Thr Glu Trp Leu Asp Leu Ser Tyr Arg Le - #u Ser Thr Gly Phe Arg                    800          - #       805          - #       810                       - - AAT CCT AGT TTT GCT GAA ATG TAT GGT TGG CG - #G TAT GGT GGC AAT AAT          4117                                                                        Asn Pro Ser Phe Ala Glu Met Tyr Gly Trp Ar - #g Tyr Gly Gly Asn Asn                815              - #   820              - #   825                           - - AGC GAT GTT TAT GTA GGT AAA TTT AAG CCT GA - #A ACA TCT CGT AAC CAA          4165                                                                        Ser Asp Val Tyr Val Gly Lys Phe Lys Pro Gl - #u Thr Ser Arg Asn Gln            830                 8 - #35                 8 - #40                 8 -       #45                                                                               - - GAG TTT GGT CTC GCT CTA AAA GGG GAT TTT GG - #T AAT ATT GAG ATC         AGT     4213                                                                     Glu Phe Gly Leu Ala Leu Lys Gly Asp Phe Gl - #y Asn Ile Glu Ile Ser                           850  - #               855  - #               860               - - CAT TTT AGT AAT GCT TAT CGA AAT CTT ATC GC - #C TTT GCT GAA GAA CTT          4261                                                                        His Phe Ser Asn Ala Tyr Arg Asn Leu Ile Al - #a Phe Ala Glu Glu Leu                        865      - #           870      - #           875                   - - AGT AAA AAT GGA ACT ACT GGA AAG GGC AAT TA - #T GGA TAT CAT AAT GCA          4309                                                                        Ser Lys Asn Gly Thr Thr Gly Lys Gly Asn Ty - #r Gly Tyr His Asn Ala                    880          - #       885          - #       890                       - - CAA AAT GCA AAA TTA GTT GGC GTA AAT ATA AC - #T GCG CAA TTA GAT TTT          4357                                                                        Gln Asn Ala Lys Leu Val Gly Val Asn Ile Th - #r Ala Gln Leu Asp Phe                895              - #   900              - #   905                           - - AAT GGT TTA TGG AAA CGT ATT CCC TAC GGT TG - #G TAT GCA ACA TTT GCT          4405                                                                        Asn Gly Leu Trp Lys Arg Ile Pro Tyr Gly Tr - #p Tyr Ala Thr Phe Ala            910                 9 - #15                 9 - #20                 9 -       #25                                                                               - - TAT AAC CGA GTA AAA GTT AAA GAT CAA AAA AT - #C AAT GCT GGT TTG         GCC     4453                                                                     Tyr Asn Arg Val Lys Val Lys Asp Gln Lys Il - #e Asn Ala Gly Leu Ala                           930  - #               935  - #               940               - - TCC GTA AGC AGT TAT TTA TTT GAT GCC ATT CA - #G CCC AGC CGT TAT ATC          4501                                                                        Ser Val Ser Ser Tyr Leu Phe Asp Ala Ile Gl - #n Pro Ser Arg Tyr Ile                        945      - #           950      - #           955                   - - ATT GGT TTA GGC TAT GAT CAT CCA AGT AAT AC - #T TGG GGA ATT AAT ACA          4549                                                                        Ile Gly Leu Gly Tyr Asp His Pro Ser Asn Th - #r Trp Gly Ile Asn Thr                    960          - #       965          - #       970                       - - ATG TTT ACT CAA TCA AAA GCA AAA TCT CAA AA - #T GAA TTG CTA GGA CAA          4597                                                                        Met Phe Thr Gln Ser Lys Ala Lys Ser Gln As - #n Glu Leu Leu Gly Gln                975              - #   980              - #   985                           - - CGT GCA TTG GGT AAC AAT TCA AGG AAT GTA AA - #A TCA ACA AGA AAA CTT          4645                                                                        Arg Ala Leu Gly Asn Asn Ser Arg Asn Val Ly - #s Ser Thr Arg Lys Leu            990                 9 - #95                 1 - #000                1005        - - ACT CGG GCA TGG CAT ATC TTA GAT GTA TCG GG - #T TAT TAC ATG GCG AAT          4693                                                                        Thr Arg Ala Trp His Ile Leu Asp Val Ser Gl - #y Tyr Tyr Met Ala Asn                            1010 - #               1015  - #              1020              - - AAA AAT ATT ATG CTT CGA TTA GGG ATA TAT AA - #T TTA TTC AAC TAT CGC          4741                                                                        Lys Asn Ile Met Leu Arg Leu Gly Ile Tyr As - #n Leu Phe Asn Tyr Arg                        1025     - #           1030      - #          1035                  - - TAT GTT ACT TGG GAA GCG GTG CGT CAA ACA GC - #A CAA GGT GCG GTC AAT          4789                                                                        Tyr Val Thr Trp Glu Ala Val Arg Gln Thr Al - #a Gln Gly Ala Val Asn                    1040         - #       1045          - #      1050                      - - CAA CAT CAA AAT GTT GGT AGC TAT ACT CGC TA - #C GCA GCA TCA GGA CGA          4837                                                                        Gln His Gln Asn Val Gly Ser Tyr Thr Arg Ty - #r Ala Ala Ser Gly Arg                1055             - #   1060              - #  1065                          - - AAC TAT ACC TTA ACA TTA GAA ATG AAA TTC TA - #AATTAAAA TGCGCCAGAT            4887                                                                        Asn Tyr Thr Leu Thr Leu Glu Met Lys Phe                                        1070                1075                                                        - - GGACTAGATA TGCTATATCT ATACCTTACT GGCGCATCTT TTTCTGTTCT AT -              #AATCTGCT   4947                                                                  - - TAAGTGAAAA ACCAAACTTG GATTTTTTAC AAGATCTTTT CACGCATTTA TT -             #GTAAAATC   5007                                                                  - - TCCGACAATT TTTACCGCAC TTTTCTCTAT TACAAAAACA ATAAGGATCC TT -             #TTGTGACT   5067                                                                  - - CTCTCAATCT TTGGCAAGTT GCTGTTACAA CTTCAGATCA AGTTTCAGCC AG -             #CGATCTTA   5127                                                                  - - GGCACTTGGG TTCGGCC             - #                  - #                       - # 5144                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO: 106:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 168 amino - #acids                                                 (B) TYPE: amino acid                                                           (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #106:                          - - Met Lys Ser Val Pro Leu Ile Ser Gly Gly Le - #u Ser Phe Leu Leu Ser         1               5 - #                 10 - #                 15               - - Ala Cys Ser Gly Gly Gly Ser Phe Asp Val As - #p Asn Val Ser Asn Pro                    20     - #             25     - #             30                   - - Ser Ser Ser Lys Pro Arg Tyr Gln Asp Asp Th - #r Ser Asn Gln Arg Thr                35         - #         40         - #         45                       - - Lys Ser Asp Leu Gln Lys Leu Ser Ile Pro Se - #r Leu Gly Gly Gly Met            50             - #     55             - #     60                           - - Lys Leu Val Ala Gln Asn Leu Leu Gly Lys Ly - #s Glu Pro Ser Leu Leu        65                 - # 70                 - # 75                 - # 80        - - Asn Asn Glu Asp Gly Tyr Met Ile Phe Ser Se - #r Leu Ser Thr Ile Glu                        85 - #                 90 - #                 95               - - Glu Asp Val Thr Lys Glu Asn Lys Ser Gln Gl - #u Pro Thr Ile Gly Ser                   100      - #           105      - #           110                   - - Ile Asp Glu Pro Ser Lys Thr Asn Ser Pro Gl - #n Asn His His Gly Asn               115          - #       120          - #       125                       - - Met Tyr Ile Arg Val Phe Ile Ile Phe Asn Ar - #g Gly Val Ile Pro Gln           130              - #   135              - #   140                           - - Met Ala Ser Phe Ile Gln Val Thr Met Asp Me - #t Arg Ile Thr Leu Ala       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Ser Lys Gln Pro Leu His Tyr Leu                                                           165                                                             - -  - - (2) INFORMATION FOR SEQ ID NO: 107:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 911 amino - #acids                                                 (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #107:                          - - Met Thr Lys Lys Pro Tyr Phe Arg Leu Ser Il - #e Ile Ser Cys Leu         Leu                                                                              1               5   - #                10  - #                15               - - Ile Ser Cys Tyr Val Lys Ala Glu Thr Gln Se - #r Ile Lys Asp Thr Lys                   20      - #            25      - #            30                    - - Glu Ala Ile Ser Ser Glu Val Asp Thr Gln Se - #r Thr Glu Asp Ser Glu               35          - #        40          - #        45                        - - Leu Glu Thr Ile Ser Val Thr Ala Glu Lys Il - #e Arg Asp Arg Lys Asp           50              - #    55              - #    60                            - - Asn Glu Val Thr Gly Leu Gly Lys Ile Ile Ly - #s Thr Ser Glu Ser Ile       65                  - #70                  - #75                  - #80         - - Ser Arg Glu Gln Val Leu Asn Ile Arg Asp Le - #u Thr Arg Tyr Asp Pro                       85  - #                90  - #                95                - - Gly Ile Ser Val Val Glu Gln Gly Arg Gly Al - #a Ser Ser Gly Tyr Ser                   100      - #           105      - #           110                   - - Ile Arg Gly Met Asp Arg Asn Arg Val Ala Le - #u Leu Val Asp Gly Leu               115          - #       120          - #       125                       - - Pro Gln Thr Gln Ser Tyr Val Val Gln Ser Pr - #o Leu Val Ala Arg Ser           130              - #   135              - #   140                           - - Gly Tyr Ser Gly Thr Gly Ala Ile Asn Glu Il - #e Glu Tyr Glu Asn Val       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Lys Ala Val Glu Ile Ser Lys Gly Gly Ser Se - #r Ser Glu Tyr Gly         Asn                                                                                              165  - #               170  - #               175              - - Gly Ala Leu Ala Gly Ser Val Thr Phe Gln Se - #r Lys Ser Ala Ala Asp                   180      - #           185      - #           190                   - - Ile Leu Glu Gly Asp Lys Ser Trp Gly Ile Gl - #n Thr Lys Asn Ala Tyr               195          - #       200          - #       205                       - - Ser Ser Lys Asn Lys Gly Phe Thr His Ser Le - #u Ala Val Ala Gly Lys           210              - #   215              - #   220                           - - Gln Gly Gly Phe Glu Gly Val Ala Ile Tyr Th - #r Gln Arg Asn Ser Glu       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Glu Thr Gln Val His Lys Asp Ala Leu Lys Gl - #y Val Gln Ser Tyr         Glu                                                                                              245  - #               250  - #               255              - - Arg Phe Ile Ala Thr Thr Asp Lys Ser Ser Gl - #y Tyr Phe Val Ile Gln                   260      - #           265      - #           270                   - - Gly Glu Cys Pro Asn Gly Asp Asp Lys Cys Al - #a Ala Lys Pro Pro Ala               275          - #       280          - #       285                       - - Lys Leu Ser Pro Gln Ser Glu Thr Val Ser Va - #l Ser Asp Tyr Thr Gly           290              - #   295              - #   300                           - - Ala Asn Arg Ile Lys Pro Asn Pro Met Lys Ty - #r Glu Ser Gln Ser Trp       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Phe Leu Arg Gly Gly Tyr His Phe Ser Glu Gl - #n His Tyr Ile Gly         Gly                                                                                              325  - #               330  - #               335              - - Ile Phe Glu Phe Thr Gln Gln Lys Phe Asp Il - #e Arg Asp Met Thr Phe                   340      - #           345      - #           350                   - - Pro Ala Tyr Leu Arg Ser Thr Glu Lys Arg As - #p Asp Arg Thr Gly Pro               355          - #       360          - #       365                       - - Phe Tyr Pro Lys Gln Asp Tyr Gly Ala Tyr Gl - #n Arg Ile Glu Asp Gly           370              - #   375              - #   380                           - - Arg Gly Val Asn Tyr Ala Ser Gly Leu Tyr Ph - #e Asp Glu His His Arg       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Lys Gln Arg Val Gly Ile Glu Tyr Ile Tyr Gl - #u Asn Lys Asn Lys         Ala                                                                                              405  - #               410  - #               415              - - Gly Ile Ile Asp Lys Ala Val Leu Ser Ala As - #n Gln Gln Asn Ile Ile                   420      - #           425      - #           430                   - - Leu Asp Ser Tyr Met Arg His Thr His Cys Se - #r Leu Tyr Pro Asn Pro               435          - #       440          - #       445                       - - Ser Lys Asn Cys Arg Pro Thr Leu Asp Lys Pr - #o Tyr Ser Tyr Tyr Arg           450              - #   455              - #   460                           - - Ser Asp Arg Asn Val Tyr Lys Glu Lys His As - #n Met Leu Gln Leu Asn       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Leu Glu Lys Lys Ile Gln Gln Asn Trp Leu Th - #r His Gln Ile Val         Phe                                                                                              485  - #               490  - #               495              - - Asn Leu Gly Phe Asp Asp Phe Thr Ser Ala Le - #u Gln His Lys Asp Tyr                   500      - #           505      - #           510                   - - Leu Thr Arg Arg Val Thr Ala Thr Ala Asn Il - #e Ile Ser Gly Thr Val               515          - #       520          - #       525                       - - Ala Gly Lys Arg Arg Asn Gly Tyr Glu Lys Gl - #n Pro Tyr Leu Tyr Ser           530              - #   535              - #   540                           - - Lys Pro Lys Val Asp Phe Val Gly Gln Asp Hi - #s Cys Asn Tyr Lys Gly       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Ser Ser Ser Asn Tyr Ser Asp Cys Lys Val Ar - #g Leu Ile Lys Gly         Lys                                                                                              565  - #               570  - #               575              - - Asn Tyr Tyr Phe Ala Ala Arg Asn Asn Met Al - #a Leu Gly Lys Tyr Ile                   580      - #           585      - #           590                   - - Asp Leu Gly Leu Gly Ile Arg Tyr Asp Val Se - #r Arg Thr Lys Ala Asn               595          - #       600          - #       605                       - - Glu Ser Thr Ile Ser Val Gly Lys Phe Lys As - #n Phe Ser Trp Asn Thr           610              - #   615              - #   620                           - - Gly Ile Val Ile Lys Pro Thr Glu Trp Leu As - #p Leu Ser Tyr Arg Leu       625                 6 - #30                 6 - #35                 6 -       #40                                                                               - - Ser Thr Gly Phe Arg Asn Pro Ser Phe Ala Gl - #u Met Tyr Gly Trp         Arg                                                                                              645  - #               650  - #               655              - - Tyr Gly Gly Asn Asn Ser Asp Val Tyr Val Gl - #y Lys Phe Lys Pro Glu                   660      - #           665      - #           670                   - - Thr Ser Arg Asn Gln Glu Phe Gly Leu Ala Le - #u Lys Gly Asp Phe Gly               675          - #       680          - #       685                       - - Asn Ile Glu Ile Ser His Phe Ser Asn Ala Ty - #r Arg Asn Leu Ile Ala           690              - #   695              - #   700                           - - Phe Ala Glu Glu Leu Ser Lys Asn Gly Thr Th - #r Gly Lys Gly Asn Tyr       705                 7 - #10                 7 - #15                 7 -       #20                                                                               - - Gly Tyr His Asn Ala Gln Asn Ala Lys Leu Va - #l Gly Val Asn Ile         Thr                                                                                              725  - #               730  - #               735              - - Ala Gln Leu Asp Phe Asn Gly Leu Trp Lys Ar - #g Ile Pro Tyr Gly Trp                   740      - #           745      - #           750                   - - Tyr Ala Thr Phe Ala Tyr Asn Arg Val Lys Va - #l Lys Asp Gln Lys Ile               755          - #       760          - #       765                       - - Asn Ala Gly Leu Ala Ser Val Ser Ser Tyr Le - #u Phe Asp Ala Ile Gln           770              - #   775              - #   780                           - - Pro Ser Arg Tyr Ile Ile Gly Leu Gly Tyr As - #p His Pro Ser Asn Thr       785                 7 - #90                 7 - #95                 8 -       #00                                                                               - - Trp Gly Ile Asn Thr Met Phe Thr Gln Ser Ly - #s Ala Lys Ser Gln         Asn                                                                                              805  - #               810  - #               815              - - Glu Leu Leu Gly Gln Arg Ala Leu Gly Asn As - #n Ser Arg Asn Val Lys                   820      - #           825      - #           830                   - - Ser Thr Arg Lys Leu Thr Arg Ala Trp His Il - #e Leu Asp Val Ser Gly               835          - #       840          - #       845                       - - Tyr Tyr Met Ala Asn Lys Asn Ile Met Leu Ar - #g Leu Gly Ile Tyr Asn           850              - #   855              - #   860                           - - Leu Phe Asn Tyr Arg Tyr Val Thr Trp Glu Al - #a Val Arg Gln Thr Ala       865                 8 - #70                 8 - #75                 8 -       #80                                                                               - - Gln Gly Ala Val Asn Gln His Gln Asn Val Gl - #y Ser Tyr Thr Arg         Tyr                                                                                              885  - #               890  - #               895              - - Ala Ala Ser Gly Arg Asn Tyr Thr Leu Thr Le - #u Glu Met Lys Phe                       900      - #           905      - #           910                   - -  - - (2) INFORMATION FOR SEQ ID NO: 108:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 1993 base - #pairs                                                 (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ix) FEATURE:                                                                   (A) NAME/KEY: CDS                                                              (B) LOCATION: 3..1946                                                 - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #108:                          - - AT ATG AAA TCT GTA CCT CTT ATC TCT GGT GGA - # CTT TCC TTT TTA TTA             47                                                                           Met Lys Ser Val Pro Leu Ile Ser Gly - #Gly Leu Ser Phe Leu Leu                   1             - #  5                - #  10                - #  15         - - AGT GCT TGT AGC GGG GGA GGT GGT TCT TTT GA - #T GTA GAT GAC GTC TCT            95                                                                        Ser Ala Cys Ser Gly Gly Gly Gly Ser Phe As - #p Val Asp Asp Val Ser                             20 - #                 25 - #                 30               - - AAT CCC TCC TCT TCT AAA CCA CGT TAT CAA GA - #C GAT ACT TCA AGT TCA           143                                                                        Asn Pro Ser Ser Ser Lys Pro Arg Tyr Gln As - #p Asp Thr Ser Ser Ser                         35     - #             40     - #             45                   - - AGA ACA AAA TCT AAA TTG GAA AAT TTG TCC AT - #T CCT TCT TTA GGG GGA           191                                                                        Arg Thr Lys Ser Lys Leu Glu Asn Leu Ser Il - #e Pro Ser Leu Gly Gly                     50         - #         55         - #         60                       - - GGG ATG AAG TTA GTG GCT CAG AAT CTT CGT GA - #T AGG ACA AAA CCT AGT           239                                                                        Gly Met Lys Leu Val Ala Gln Asn Leu Arg As - #p Arg Thr Lys Pro Ser                 65             - #     70             - #     75                           - - CTC TTA AAT GAA GAT GAC TAT ATG ATA TTT TC - #C TCA CTT TCA ACG ATT           287                                                                        Leu Leu Asn Glu Asp Asp Tyr Met Ile Phe Se - #r Ser Leu Ser Thr Ile             80                 - # 85                 - # 90                 - # 95        - - AAA GCT GAT GTT GAA AAA GAA AAT AAA CAC TA - #T ACA AGT CCA GTT GGC           335                                                                        Lys Ala Asp Val Glu Lys Glu Asn Lys His Ty - #r Thr Ser Pro Val Gly                            100  - #               105  - #               110               - - TCA ATA GAC GAG CCT AGT ACA ACA AAT CCA AA - #A GAA AAT GAT CAT GGA           383                                                                        Ser Ile Asp Glu Pro Ser Thr Thr Asn Pro Ly - #s Glu Asn Asp His Gly                        115      - #           120      - #           125                   - - CAA AGA TAT GTA TAT TCA GGA CTT TAT TAT AT - #T CCA TCG TGG AAT TTA           431                                                                        Gln Arg Tyr Val Tyr Ser Gly Leu Tyr Tyr Il - #e Pro Ser Trp Asn Leu                    130          - #       135          - #       140                       - - AAC GAT CTT AAA AAT AAC AAG TAT TAT TAT TC - #T GGT TAC TAT GGA TAT           479                                                                        Asn Asp Leu Lys Asn Asn Lys Tyr Tyr Tyr Se - #r Gly Tyr Tyr Gly Tyr                145              - #   150              - #   155                           - - GCG TAT TAC TTT GGC AAG CAA ACA GCC ACT AC - #A TTA CCT GTA AAT GGC           527                                                                        Ala Tyr Tyr Phe Gly Lys Gln Thr Ala Thr Th - #r Leu Pro Val Asn Gly            160                 1 - #65                 1 - #70                 1 -       #75                                                                               - - AAA GTA ACG TAT AAA GGA ACT TGG AGC TTC AT - #C ACC GCA GCT GAA         AAT      575                                                                     Lys Val Thr Tyr Lys Gly Thr Trp Ser Phe Il - #e Thr Ala Ala Glu Asn                           180  - #               185  - #               190               - - GGC AAA AGG TAT CCT TTG TTA AGT AAT GGC AG - #T CAA GCT TAT TTT CGA           623                                                                        Gly Lys Arg Tyr Pro Leu Leu Ser Asn Gly Se - #r Gln Ala Tyr Phe Arg                        195      - #           200      - #           205                   - - CGT AGT GCA ATT CCA GAA GAT ATT GAT TTA GA - #A GTT AAA AAT GAT GAG           671                                                                        Arg Ser Ala Ile Pro Glu Asp Ile Asp Leu Gl - #u Val Lys Asn Asp Glu                    210          - #       215          - #       220                       - - AAT AGA GAA AAA GGG CTA GTG AGT GAA TTT AG - #T GCA GAT TTT GGG ACT           719                                                                        Asn Arg Glu Lys Gly Leu Val Ser Glu Phe Se - #r Ala Asp Phe Gly Thr                225              - #   230              - #   235                           - - AAA AAA CTG ACA GGA GGA CTG TTT TAC ACC AA - #A AGA CAA ACT CAT ATT           767                                                                        Lys Lys Leu Thr Gly Gly Leu Phe Tyr Thr Ly - #s Arg Gln Thr His Ile            240                 2 - #45                 2 - #50                 2 -       #55                                                                               - - CAA AAC CAT GAA AAG AAA AAA CTC TAT GAT AT - #A GAT GCC CAT ATT         TAT      815                                                                     Gln Asn His Glu Lys Lys Lys Leu Tyr Asp Il - #e Asp Ala His Ile Tyr                           260  - #               265  - #               270               - - AGT AAT AGA TTC AGA GGT AAA GTA AAT CCT AC - #C CAA AAA GAT TCT AAA           863                                                                        Ser Asn Arg Phe Arg Gly Lys Val Asn Pro Th - #r Gln Lys Asp Ser Lys                        275      - #           280      - #           285                   - - GAA CAT CCC TTT ACC AGC GAG GGA ACA TTA GA - #A GGT GGT TTT TAC GGG           911                                                                        Glu His Pro Phe Thr Ser Glu Gly Thr Leu Gl - #u Gly Gly Phe Tyr Gly                    290          - #       295          - #       300                       - - CCT GAA GGT CAA GAA TTA GGA GGA AAG TTT TT - #A GCT GGC GAC AAA AAA           959                                                                        Pro Glu Gly Gln Glu Leu Gly Gly Lys Phe Le - #u Ala Gly Asp Lys Lys                305              - #   310              - #   315                           - - GTT TTT GGG GTA TTT AGT GCC AAA GGA ACG GA - #A GAA AAC AAA AAA TTA          1007                                                                        Val Phe Gly Val Phe Ser Ala Lys Gly Thr Gl - #u Glu Asn Lys Lys Leu            320                 3 - #25                 3 - #30                 3 -       #35                                                                               - - CCC AAA GAA ACC TTA ATT GAT GGC AAG CTA AC - #T ACT TTC TCT ACT         AAA     1055                                                                     Pro Lys Glu Thr Leu Ile Asp Gly Lys Leu Th - #r Thr Phe Ser Thr Lys                           340  - #               345  - #               350               - - ACA ACC GAT GCA AAA ACC AAT GCA ACA GCC AA - #T GCA ACA ACC AGT ACC          1103                                                                        Thr Thr Asp Ala Lys Thr Asn Ala Thr Ala As - #n Ala Thr Thr Ser Thr                        355      - #           360      - #           365                   - - GCA GCC AAT ACA ACA ACC GAT ACA ACA GCC AA - #T ACA ATA ACC GAT GCA          1151                                                                        Ala Ala Asn Thr Thr Thr Asp Thr Thr Ala As - #n Thr Ile Thr Asp Ala                    370          - #       375          - #       380                       - - GAA AAC TTT AAG ACG AAA GAT ATA TCA AGT TT - #T GGT GAA GCT GAT TAC          1199                                                                        Glu Asn Phe Lys Thr Lys Asp Ile Ser Ser Ph - #e Gly Glu Ala Asp Tyr                385              - #   390              - #   395                           - - CTT TTA ATT GAT AAT TAC CCT GTT CCT CTT TT - #A CCT GAG AGT GGT GAT          1247                                                                        Leu Leu Ile Asp Asn Tyr Pro Val Pro Leu Le - #u Pro Glu Ser Gly Asp            400                 4 - #05                 4 - #10                 4 -       #15                                                                               - - TTC ATA AGT AGT AAG CAC CAT ACT GTA GGA AA - #G AAA ACC TAT CAA         GTA     1295                                                                     Phe Ile Ser Ser Lys His His Thr Val Gly Ly - #s Lys Thr Tyr Gln Val                           420  - #               425  - #               430               - - AAA GCA TGT TGC AGT AAT CTA AGC TAT GTG AA - #A TTT GGT ATG TAT TAT          1343                                                                        Lys Ala Cys Cys Ser Asn Leu Ser Tyr Val Ly - #s Phe Gly Met Tyr Tyr                        435      - #           440      - #           445                   - - GAA GTC CCA CCT AAA GAA GAA GAA AAA GAC AA - #A GAA AAA AAA GAA AAA          1391                                                                        Glu Val Pro Pro Lys Glu Glu Glu Lys Asp Ly - #s Glu Lys Lys Glu Lys                    450          - #       455          - #       460                       - - GAA AAA GAA AAA CAA GCG ACA AAT CTA TCG AA - #C ACT TAT TAT CAA TTC          1439                                                                        Glu Lys Glu Lys Gln Ala Thr Asn Leu Ser As - #n Thr Tyr Tyr Gln Phe                465              - #   470              - #   475                           - - TTA TTA GGT CTC CGT ACT CCC AGT TCT GAA AT - #T CCT AAA GGA GGA AGT          1487                                                                        Leu Leu Gly Leu Arg Thr Pro Ser Ser Glu Il - #e Pro Lys Gly Gly Ser            480                 4 - #85                 4 - #90                 4 -       #95                                                                               - - GCA AAA TAT CTC GGT AGT TGG TTT GGT TAT CT - #G AGC GAT GGT TCA         ACA     1535                                                                     Ala Lys Tyr Leu Gly Ser Trp Phe Gly Tyr Le - #u Ser Asp Gly Ser Thr                           500  - #               505  - #               510               - - TCT TAC TCC CCC AGT GGT GAT AAG AAA CGC GA - #G AAC AAT GCT CTC GCC          1583                                                                        Ser Tyr Ser Pro Ser Gly Asp Lys Lys Arg Gl - #u Asn Asn Ala Leu Ala                        515      - #           520      - #           525                   - - GAG TTT AAT GTA AAT TTT GTC GAT AAA ACA TT - #A AAA GGC CAA TTA ATA          1631                                                                        Glu Phe Asn Val Asn Phe Val Asp Lys Thr Le - #u Lys Gly Gln Leu Ile                    530          - #       535          - #       540                       - - CGA CAC GAT AAT CAA AAT ACC GTT TTT ACA AT - #T GAT GCA ACC TTT AAA          1679                                                                        Arg His Asp Asn Gln Asn Thr Val Phe Thr Il - #e Asp Ala Thr Phe Lys                545              - #   550              - #   555                           - - GGT GGT AAG AAT AAC TTC ACT GGT ACA GCA AC - #C GCA AAC AAT GTA GCG          1727                                                                        Gly Gly Lys Asn Asn Phe Thr Gly Thr Ala Th - #r Ala Asn Asn Val Ala            560                 5 - #65                 5 - #70                 5 -       #75                                                                               - - ATT GAT CCC CAA AGT ACA CAA GGC ACA TCT AA - #C GTC AAT TTC ACG         GCA     1775                                                                     Ile Asp Pro Gln Ser Thr Gln Gly Thr Ser As - #n Val Asn Phe Thr Ala                           580  - #               585  - #               590               - - ACA GTA AAT GGG GCA TTT TAT GGG CCG AAC GC - #T ACA GAA TTA GGC GGT          1823                                                                        Thr Val Asn Gly Ala Phe Tyr Gly Pro Asn Al - #a Thr Glu Leu Gly Gly                        595      - #           600      - #           605                   - - TAT TTC ACC TAT AAC GGA AAT CCT ACA GAT AA - #A AGT TCC TCA ACC GTA          1871                                                                        Tyr Phe Thr Tyr Asn Gly Asn Pro Thr Asp Ly - #s Ser Ser Ser Thr Val                    610          - #       615          - #       620                       - - CCT TCA TCA TCC AAT TCA AAA AAT GCA AGA GC - #T GCA GTT GTC TTT GGT          1919                                                                        Pro Ser Ser Ser Asn Ser Lys Asn Ala Arg Al - #a Ala Val Val Phe Gly                625              - #   630              - #   635                           - - GCG AGA CAA CAA GTA GAA ACA ACC AAA TAATGGAAT - #A CTAAAAATGA                1966                                                                        Ala Arg Gln Gln Val Glu Thr Thr Lys                                            640                 6 - #45                                                     - - CTAAAAAAGC TTCTAGAAGC CGAATTC          - #                  - #                1993                                                                       - -  - - (2) INFORMATION FOR SEQ ID NO: 109:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 648 amino - #acids                                                 (B) TYPE: amino acid                                                           (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #109:                          - - Met Lys Ser Val Pro Leu Ile Ser Gly Gly Le - #u Ser Phe Leu Leu Ser         1               5 - #                 10 - #                 15               - - Ala Cys Ser Gly Gly Gly Gly Ser Phe Asp Va - #l Asp Asp Val Ser Asn                    20     - #             25     - #             30                   - - Pro Ser Ser Ser Lys Pro Arg Tyr Gln Asp As - #p Thr Ser Ser Ser Arg                35         - #         40         - #         45                       - - Thr Lys Ser Lys Leu Glu Asn Leu Ser Ile Pr - #o Ser Leu Gly Gly Gly            50             - #     55             - #     60                           - - Met Lys Leu Val Ala Gln Asn Leu Arg Asp Ar - #g Thr Lys Pro Ser Leu        65                 - # 70                 - # 75                 - # 80        - - Leu Asn Glu Asp Asp Tyr Met Ile Phe Ser Se - #r Leu Ser Thr Ile Lys                        85 - #                 90 - #                 95               - - Ala Asp Val Glu Lys Glu Asn Lys His Tyr Th - #r Ser Pro Val Gly Ser                   100      - #           105      - #           110                   - - Ile Asp Glu Pro Ser Thr Thr Asn Pro Lys Gl - #u Asn Asp His Gly Gln               115          - #       120          - #       125                       - - Arg Tyr Val Tyr Ser Gly Leu Tyr Tyr Ile Pr - #o Ser Trp Asn Leu Asn           130              - #   135              - #   140                           - - Asp Leu Lys Asn Asn Lys Tyr Tyr Tyr Ser Gl - #y Tyr Tyr Gly Tyr Ala       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Tyr Tyr Phe Gly Lys Gln Thr Ala Thr Thr Le - #u Pro Val Asn Gly         Lys                                                                                              165  - #               170  - #               175              - - Val Thr Tyr Lys Gly Thr Trp Ser Phe Ile Th - #r Ala Ala Glu Asn Gly                   180      - #           185      - #           190                   - - Lys Arg Tyr Pro Leu Leu Ser Asn Gly Ser Gl - #n Ala Tyr Phe Arg Arg               195          - #       200          - #       205                       - - Ser Ala Ile Pro Glu Asp Ile Asp Leu Glu Va - #l Lys Asn Asp Glu Asn           210              - #   215              - #   220                           - - Arg Glu Lys Gly Leu Val Ser Glu Phe Ser Al - #a Asp Phe Gly Thr Lys       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Lys Leu Thr Gly Gly Leu Phe Tyr Thr Lys Ar - #g Gln Thr His Ile         Gln                                                                                              245  - #               250  - #               255              - - Asn His Glu Lys Lys Lys Leu Tyr Asp Ile As - #p Ala His Ile Tyr Ser                   260      - #           265      - #           270                   - - Asn Arg Phe Arg Gly Lys Val Asn Pro Thr Gl - #n Lys Asp Ser Lys Glu               275          - #       280          - #       285                       - - His Pro Phe Thr Ser Glu Gly Thr Leu Glu Gl - #y Gly Phe Tyr Gly Pro           290              - #   295              - #   300                           - - Glu Gly Gln Glu Leu Gly Gly Lys Phe Leu Al - #a Gly Asp Lys Lys Val       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Phe Gly Val Phe Ser Ala Lys Gly Thr Glu Gl - #u Asn Lys Lys Leu         Pro                                                                                              325  - #               330  - #               335              - - Lys Glu Thr Leu Ile Asp Gly Lys Leu Thr Th - #r Phe Ser Thr Lys Thr                   340      - #           345      - #           350                   - - Thr Asp Ala Lys Thr Asn Ala Thr Ala Asn Al - #a Thr Thr Ser Thr Ala               355          - #       360          - #       365                       - - Ala Asn Thr Thr Thr Asp Thr Thr Ala Asn Th - #r Ile Thr Asp Ala Glu           370              - #   375              - #   380                           - - Asn Phe Lys Thr Lys Asp Ile Ser Ser Phe Gl - #y Glu Ala Asp Tyr Leu       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Leu Ile Asp Asn Tyr Pro Val Pro Leu Leu Pr - #o Glu Ser Gly Asp         Phe                                                                                              405  - #               410  - #               415              - - Ile Ser Ser Lys His His Thr Val Gly Lys Ly - #s Thr Tyr Gln Val Lys                   420      - #           425      - #           430                   - - Ala Cys Cys Ser Asn Leu Ser Tyr Val Lys Ph - #e Gly Met Tyr Tyr Glu               435          - #       440          - #       445                       - - Val Pro Pro Lys Glu Glu Glu Lys Asp Lys Gl - #u Lys Lys Glu Lys Glu           450              - #   455              - #   460                           - - Lys Glu Lys Gln Ala Thr Asn Leu Ser Asn Th - #r Tyr Tyr Gln Phe Leu       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Leu Gly Leu Arg Thr Pro Ser Ser Glu Ile Pr - #o Lys Gly Gly Ser         Ala                                                                                              485  - #               490  - #               495              - - Lys Tyr Leu Gly Ser Trp Phe Gly Tyr Leu Se - #r Asp Gly Ser Thr Ser                   500      - #           505      - #           510                   - - Tyr Ser Pro Ser Gly Asp Lys Lys Arg Glu As - #n Asn Ala Leu Ala Glu               515          - #       520          - #       525                       - - Phe Asn Val Asn Phe Val Asp Lys Thr Leu Ly - #s Gly Gln Leu Ile Arg           530              - #   535              - #   540                           - - His Asp Asn Gln Asn Thr Val Phe Thr Ile As - #p Ala Thr Phe Lys Gly       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Gly Lys Asn Asn Phe Thr Gly Thr Ala Thr Al - #a Asn Asn Val Ala         Ile                                                                                              565  - #               570  - #               575              - - Asp Pro Gln Ser Thr Gln Gly Thr Ser Asn Va - #l Asn Phe Thr Ala Thr                   580      - #           585      - #           590                   - - Val Asn Gly Ala Phe Tyr Gly Pro Asn Ala Th - #r Glu Leu Gly Gly Tyr               595          - #       600          - #       605                       - - Phe Thr Tyr Asn Gly Asn Pro Thr Asp Lys Se - #r Ser Ser Thr Val Pro           610              - #   615              - #   620                           - - Ser Ser Ser Asn Ser Lys Asn Ala Arg Ala Al - #a Val Val Phe Gly Ala       625                 6 - #30                 6 - #35                 6 -       #40                                                                               - - Arg Gln Gln Val Glu Thr Thr Lys                                                           645                                                             - -  - - (2) INFORMATION FOR SEQ ID NO: 110:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 1974 base - #pairs                                                 (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ix) FEATURE:                                                                   (A) NAME/KEY: CDS                                                              (B) LOCATION: 20..1912                                                - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #110:                          - - GAATTCGGCT TGGATCCAT ATG AAA TCT GTA CCT CTT ATC - # TCT GGT GGA        CTT      52                                                                                        - #   Met Lys Ser Val Pro Leu Ile Ser Gly - # Gly Leu                         - #     1             - #  5                - #  10           - - TCC TTT TTA CTA AGT GCT TGT AGC GGA GGG GG - #G TCT TTT GAT GTA GAT           100                                                                        Ser Phe Leu Leu Ser Ala Cys Ser Gly Gly Gl - #y Ser Phe Asp Val Asp                         15     - #             20     - #             25                   - - AAC GTC TCT AAT CCA TCC TCT TCT AAA CCA CG - #T TAT CAA GAC GAT ACT           148                                                                        Asn Val Ser Asn Pro Ser Ser Ser Lys Pro Ar - #g Tyr Gln Asp Asp Thr                     30         - #         35         - #         40                       - - TCA AGT TCA AGA ACA AAA TCT AAT TTG AAA AA - #G TTG TCC ATT CCT TCT           196                                                                        Ser Ser Ser Arg Thr Lys Ser Asn Leu Lys Ly - #s Leu Ser Ile Pro Ser                 45             - #     50             - #     55                           - - TTA GGG GGA GGG ATG AAG TTA GTG GCT CAG AA - #T CTT AGT GAT AAG AAC           244                                                                        Leu Gly Gly Gly Met Lys Leu Val Ala Gln As - #n Leu Ser Asp Lys Asn             60                 - # 65                 - # 70                 - # 75        - - AAA CCT AGT CTC TTA AAT GAA GAT GAC TAT AT - #A TCA TAT TTT TCC TCA           292                                                                        Lys Pro Ser Leu Leu Asn Glu Asp Asp Tyr Il - #e Ser Tyr Phe Ser Ser                             80 - #                 85 - #                 90               - - CTT TCT ACA ATT CAA GAT GAT GTT AAA AAA GA - #A AAT AAA CGC CAT ACA           340                                                                        Leu Ser Thr Ile Gln Asp Asp Val Lys Lys Gl - #u Asn Lys Arg His Thr                         95     - #            100     - #            105                   - - AAT CCA GTT GGC TCA ATA GAC GAG CCT AAC GC - #A ACA AAT CCA CCC GAA           388                                                                        Asn Pro Val Gly Ser Ile Asp Glu Pro Asn Al - #a Thr Asn Pro Pro Glu                    110          - #       115          - #       120                       - - AAG CAT CAT GGA CAA AGA TAT GTA TAT TCA GG - #G CTT TAT TAT ATT CCA           436                                                                        Lys His His Gly Gln Arg Tyr Val Tyr Ser Gl - #y Leu Tyr Tyr Ile Pro                125              - #   130              - #   135                           - - TCG TGG AGT CAT TCC TCA AAT GGC AAG CTT TA - #T TTA GGT TAC TAT GGA           484                                                                        Ser Trp Ser His Ser Ser Asn Gly Lys Leu Ty - #r Leu Gly Tyr Tyr Gly            140                 1 - #45                 1 - #50                 1 -       #55                                                                               - - TAT GCG TTT TAT TAT GGT AAT AAA ACT GCA AC - #A AAC TTG CCA GTA         AGC      532                                                                     Tyr Ala Phe Tyr Tyr Gly Asn Lys Thr Ala Th - #r Asn Leu Pro Val Ser                           160  - #               165  - #               170               - - GGC ATA GCT AAA TAC AAA GGA ACT TGG GAT TT - #T ATT ACT GCA ACT AAA           580                                                                        Gly Ile Ala Lys Tyr Lys Gly Thr Trp Asp Ph - #e Ile Thr Ala Thr Lys                        175      - #           180      - #           185                   - - AAT GGC CAA CGT TAT TCT TTA TTT GGT AGC GC - #T TTT GGA GCT TAT AAT           628                                                                        Asn Gly Gln Arg Tyr Ser Leu Phe Gly Ser Al - #a Phe Gly Ala Tyr Asn                    190          - #       195          - #       200                       - - AGA CGC AGT GCT ATT TCA GAA GAT ATA GAT AA - #T TTA GAA AAT AAT CTA           676                                                                        Arg Arg Ser Ala Ile Ser Glu Asp Ile Asp As - #n Leu Glu Asn Asn Leu                205              - #   210              - #   215                           - - AAG AAT GGT GCG GGA TTA ACT AGT GAA TTT AC - #T GTC AAT TTT GGT ACG           724                                                                        Lys Asn Gly Ala Gly Leu Thr Ser Glu Phe Th - #r Val Asn Phe Gly Thr            220                 2 - #25                 2 - #30                 2 -       #35                                                                               - - AAA AAG CTC ACT GGA AAA CTT TAT TAT AAT GA - #A AGG GAA ACA AAT         CTT      772                                                                     Lys Lys Leu Thr Gly Lys Leu Tyr Tyr Asn Gl - #u Arg Glu Thr Asn Leu                           240  - #               245  - #               250               - - AAT AAA TTA CAA AAG AGA AAA CAT GAA CTC TA - #T GAT ATA GAT GCC GAT           820                                                                        Asn Lys Leu Gln Lys Arg Lys His Glu Leu Ty - #r Asp Ile Asp Ala Asp                        255      - #           260      - #           265                   - - ATT TAT AGT AAT AGA TTC AGA GGT AAA GTA AA - #G CCA ACA ACC CAA AAA           868                                                                        Ile Tyr Ser Asn Arg Phe Arg Gly Lys Val Ly - #s Pro Thr Thr Gln Lys                    270          - #       275          - #       280                       - - GAT TCT CAA GAA CAT CCC TTT ACC AGC GAG GG - #A ACA TTA GAA GGT GGT           916                                                                        Asp Ser Gln Glu His Pro Phe Thr Ser Glu Gl - #y Thr Leu Glu Gly Gly                285              - #   290              - #   295                           - - TTT TAT GGG CCT AAC GGT GAA GAA TTA GGA GG - #A AAG TTT TTA GCT GGC           964                                                                        Phe Tyr Gly Pro Asn Gly Glu Glu Leu Gly Gl - #y Lys Phe Leu Ala Gly            300                 3 - #05                 3 - #10                 3 -       #15                                                                               - - GAT AAC CGA GTT TTT GGG GTA TTT AGT GCC AA - #A GAA GAA GAA ACA         AAA     1012                                                                     Asp Asn Arg Val Phe Gly Val Phe Ser Ala Ly - #s Glu Glu Glu Thr Lys                           320  - #               325  - #               330               - - GAC AAA AAA TTA TCC AGA GAA ACC TTA ATT GA - #T GGC AAG CTA ATT ACT          1060                                                                        Asp Lys Lys Leu Ser Arg Glu Thr Leu Ile As - #p Gly Lys Leu Ile Thr                        335      - #           340      - #           345                   - - TTT AAA AGA ACT GAT GCA ACA ACC AAT ACA GC - #A GCC AAT GCA AAA ACC          1108                                                                        Phe Lys Arg Thr Asp Ala Thr Thr Asn Thr Al - #a Ala Asn Ala Lys Thr                    350          - #       355          - #       360                       - - GAT GAA AAA AAC TTT ACG ACG AAA GAT ATA CC - #A AGT TTT GGT GAA GCT          1156                                                                        Asp Glu Lys Asn Phe Thr Thr Lys Asp Ile Pr - #o Ser Phe Gly Glu Ala                365              - #   370              - #   375                           - - GAT TAC CTT TTA ATT GAT AAT TAC CCT GTT CC - #T CTT TTC CCT GAA GAA          1204                                                                        Asp Tyr Leu Leu Ile Asp Asn Tyr Pro Val Pr - #o Leu Phe Pro Glu Glu            380                 3 - #85                 3 - #90                 3 -       #95                                                                               - - AAT ACT AAT GAT TTC ATA ACT AGT AGG CAC CA - #T AAG GTA GGA GAT         AAA     1252                                                                     Asn Thr Asn Asp Phe Ile Thr Ser Arg His Hi - #s Lys Val Gly Asp Lys                           400  - #               405  - #               410               - - ACC TAT AAA GTA GAA GCA TGT TGC AAG AAT CT - #A AGC TAT GTG AAA TTT          1300                                                                        Thr Tyr Lys Val Glu Ala Cys Cys Lys Asn Le - #u Ser Tyr Val Lys Phe                        415      - #           420      - #           425                   - - GGT ATG TAT TAT GAA GAC CCA TTA AAT GGA GA - #A AAT GGC AAA GAA AAA          1348                                                                        Gly Met Tyr Tyr Glu Asp Pro Leu Asn Gly Gl - #u Asn Gly Lys Glu Lys                    430          - #       435          - #       440                       - - GAA AAA GAA AAA GAA AAA GAC AAA GAA AAA CA - #A GCG ACA ACA TCT ATC          1396                                                                        Glu Lys Glu Lys Glu Lys Asp Lys Glu Lys Gl - #n Ala Thr Thr Ser Ile                445              - #   450              - #   455                           - - AAG ACT TAT TAT CAA TTC TTA TTA GGT CAC CG - #T ACT GCC AAG GCC GAC          1444                                                                        Lys Thr Tyr Tyr Gln Phe Leu Leu Gly His Ar - #g Thr Ala Lys Ala Asp            460                 4 - #65                 4 - #70                 4 -       #75                                                                               - - ATA CCT GCA ACG GGA AAC GTG AAA TAT CGC GG - #T AAT TGG TTT GGT         TAT     1492                                                                     Ile Pro Ala Thr Gly Asn Val Lys Tyr Arg Gl - #y Asn Trp Phe Gly Tyr                           480  - #               485  - #               490               - - ATT GGT GAT GAC AAG ACA TCT TAC TCC ACT AC - #T GGA GAT AAA AAT GCT          1540                                                                        Ile Gly Asp Asp Lys Thr Ser Tyr Ser Thr Th - #r Gly Asp Lys Asn Ala                        495      - #           500      - #           505                   - - GTC GCC GAG TTT GAT GTA AAT TTT GCC GAT AA - #A ACA TTA ACA GGC ACA          1588                                                                        Val Ala Glu Phe Asp Val Asn Phe Ala Asp Ly - #s Thr Leu Thr Gly Thr                    510          - #       515          - #       520                       - - TTA AAA CGA CAC GAT AAT GGA AAT CCC GTA TT - #T ACA ATT AAT GCA AGC          1636                                                                        Leu Lys Arg His Asp Asn Gly Asn Pro Val Ph - #e Thr Ile Asn Ala Ser                525              - #   530              - #   535                           - - TTT CAA AGT GGT AAG AAT GAC TTC ACT GGT AC - #A GCA ACC GCA AAC AAT          1684                                                                        Phe Gln Ser Gly Lys Asn Asp Phe Thr Gly Th - #r Ala Thr Ala Asn Asn            540                 5 - #45                 5 - #50                 5 -       #55                                                                               - - GTA GCG ATT GAT CCC CAA AAT ACA CAA ACC AC - #A TCT AGA GTC AAT         TTC     1732                                                                     Val Ala Ile Asp Pro Gln Asn Thr Gln Thr Th - #r Ser Arg Val Asn Phe                           560  - #               565  - #               570               - - ACG GCA ACA GTA AAC GGG GCA TTT TAT GGA CC - #T AAG GCT ACA GAA TTA          1780                                                                        Thr Ala Thr Val Asn Gly Ala Phe Tyr Gly Pr - #o Lys Ala Thr Glu Leu                        575      - #           580      - #           585                   - - GGC GGT TAT TTC ACT TAT AAC GGA AAC AAT CC - #T ACA GAT AAA AAT TCC          1828                                                                        Gly Gly Tyr Phe Thr Tyr Asn Gly Asn Asn Pr - #o Thr Asp Lys Asn Ser                    590          - #       595          - #       600                       - - TCA ACC GTT TCA CCA TCC AAT TCA GCA AAT GC - #T CGT GCT GCC GTT GTG          1876                                                                        Ser Thr Val Ser Pro Ser Asn Ser Ala Asn Al - #a Arg Ala Ala Val Val                605              - #   610              - #   615                           - - TTT GGC GCT AAA AAA CAA GTA GAA ACA ACC AA - #C AAG TAAAAACAAC               1922                                                                        Phe Gly Ala Lys Lys Gln Val Glu Thr Thr As - #n Lys                            620                 6 - #25                 6 - #30                             - - CAAGTAATGG AATACTAAAA ATGACTAAAA AAGCTTCTAG AAAGCCGAAT TC - #                1974                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO: 111:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 631 amino - #acids                                                 (B) TYPE: amino acid                                                           (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #111:                          - - Met Lys Ser Val Pro Leu Ile Ser Gly Gly Le - #u Ser Phe Leu Leu Ser         1               5 - #                 10 - #                 15               - - Ala Cys Ser Gly Gly Gly Ser Phe Asp Val As - #p Asn Val Ser Asn Pro                    20     - #             25     - #             30                   - - Ser Ser Ser Lys Pro Arg Tyr Gln Asp Asp Th - #r Ser Ser Ser Arg Thr                35         - #         40         - #         45                       - - Lys Ser Asn Leu Lys Lys Leu Ser Ile Pro Se - #r Leu Gly Gly Gly Met            50             - #     55             - #     60                           - - Lys Leu Val Ala Gln Asn Leu Ser Asp Lys As - #n Lys Pro Ser Leu Leu        65                 - # 70                 - # 75                 - # 80        - - Asn Glu Asp Asp Tyr Ile Ser Tyr Phe Ser Se - #r Leu Ser Thr Ile Gln                        85 - #                 90 - #                 95               - - Asp Asp Val Lys Lys Glu Asn Lys Arg His Th - #r Asn Pro Val Gly Ser                   100      - #           105      - #           110                   - - Ile Asp Glu Pro Asn Ala Thr Asn Pro Pro Gl - #u Lys His His Gly Gln               115          - #       120          - #       125                       - - Arg Tyr Val Tyr Ser Gly Leu Tyr Tyr Ile Pr - #o Ser Trp Ser His Ser           130              - #   135              - #   140                           - - Ser Asn Gly Lys Leu Tyr Leu Gly Tyr Tyr Gl - #y Tyr Ala Phe Tyr Tyr       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Gly Asn Lys Thr Ala Thr Asn Leu Pro Val Se - #r Gly Ile Ala Lys         Tyr                                                                                              165  - #               170  - #               175              - - Lys Gly Thr Trp Asp Phe Ile Thr Ala Thr Ly - #s Asn Gly Gln Arg Tyr                   180      - #           185      - #           190                   - - Ser Leu Phe Gly Ser Ala Phe Gly Ala Tyr As - #n Arg Arg Ser Ala Ile               195          - #       200          - #       205                       - - Ser Glu Asp Ile Asp Asn Leu Glu Asn Asn Le - #u Lys Asn Gly Ala Gly           210              - #   215              - #   220                           - - Leu Thr Ser Glu Phe Thr Val Asn Phe Gly Th - #r Lys Lys Leu Thr Gly       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Lys Leu Tyr Tyr Asn Glu Arg Glu Thr Asn Le - #u Asn Lys Leu Gln         Lys                                                                                              245  - #               250  - #               255              - - Arg Lys His Glu Leu Tyr Asp Ile Asp Ala As - #p Ile Tyr Ser Asn Arg                   260      - #           265      - #           270                   - - Phe Arg Gly Lys Val Lys Pro Thr Thr Gln Ly - #s Asp Ser Gln Glu His               275          - #       280          - #       285                       - - Pro Phe Thr Ser Glu Gly Thr Leu Glu Gly Gl - #y Phe Tyr Gly Pro Asn           290              - #   295              - #   300                           - - Gly Glu Glu Leu Gly Gly Lys Phe Leu Ala Gl - #y Asp Asn Arg Val Phe       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Gly Val Phe Ser Ala Lys Glu Glu Glu Thr Ly - #s Asp Lys Lys Leu         Ser                                                                                              325  - #               330  - #               335              - - Arg Glu Thr Leu Ile Asp Gly Lys Leu Ile Th - #r Phe Lys Arg Thr Asp                   340      - #           345      - #           350                   - - Ala Thr Thr Asn Thr Ala Ala Asn Ala Lys Th - #r Asp Glu Lys Asn Phe               355          - #       360          - #       365                       - - Thr Thr Lys Asp Ile Pro Ser Phe Gly Glu Al - #a Asp Tyr Leu Leu Ile           370              - #   375              - #   380                           - - Asp Asn Tyr Pro Val Pro Leu Phe Pro Glu Gl - #u Asn Thr Asn Asp Phe       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Ile Thr Ser Arg His His Lys Val Gly Asp Ly - #s Thr Tyr Lys Val         Glu                                                                                              405  - #               410  - #               415              - - Ala Cys Cys Lys Asn Leu Ser Tyr Val Lys Ph - #e Gly Met Tyr Tyr Glu                   420      - #           425      - #           430                   - - Asp Pro Leu Asn Gly Glu Asn Gly Lys Glu Ly - #s Glu Lys Glu Lys Glu               435          - #       440          - #       445                       - - Lys Asp Lys Glu Lys Gln Ala Thr Thr Ser Il - #e Lys Thr Tyr Tyr Gln           450              - #   455              - #   460                           - - Phe Leu Leu Gly His Arg Thr Ala Lys Ala As - #p Ile Pro Ala Thr Gly       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Asn Val Lys Tyr Arg Gly Asn Trp Phe Gly Ty - #r Ile Gly Asp Asp         Lys                                                                                              485  - #               490  - #               495              - - Thr Ser Tyr Ser Thr Thr Gly Asp Lys Asn Al - #a Val Ala Glu Phe Asp                   500      - #           505      - #           510                   - - Val Asn Phe Ala Asp Lys Thr Leu Thr Gly Th - #r Leu Lys Arg His Asp               515          - #       520          - #       525                       - - Asn Gly Asn Pro Val Phe Thr Ile Asn Ala Se - #r Phe Gln Ser Gly Lys           530              - #   535              - #   540                           - - Asn Asp Phe Thr Gly Thr Ala Thr Ala Asn As - #n Val Ala Ile Asp Pro       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Gln Asn Thr Gln Thr Thr Ser Arg Val Asn Ph - #e Thr Ala Thr Val         Asn                                                                                              565  - #               570  - #               575              - - Gly Ala Phe Tyr Gly Pro Lys Ala Thr Glu Le - #u Gly Gly Tyr Phe Thr                   580      - #           585      - #           590                   - - Tyr Asn Gly Asn Asn Pro Thr Asp Lys Asn Se - #r Ser Thr Val Ser Pro               595          - #       600          - #       605                       - - Ser Asn Ser Ala Asn Ala Arg Ala Ala Val Va - #l Phe Gly Ala Lys Lys           610              - #   615              - #   620                           - - Gln Val Glu Thr Thr Asn Lys                                               625                 6 - #30                                                     - -  - - (2) INFORMATION FOR SEQ ID NO: 112:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 1951 base - #pairs                                                 (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ix) FEATURE:                                                                   (A) NAME/KEY: CDS                                                              (B) LOCATION: 1..1890                                                 - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #112:                          - - ATG AAA TCT GTA CCT CTT ATC TCT GGT GGA CT - #T TCC CTT TTA TTA AGT            48                                                                        Met Lys Ser Val Pro Leu Ile Ser Gly Gly Le - #u Ser Leu Leu Leu Ser              1               5 - #                 10 - #                 15               - - GCT TGT AGC GGG GGA GGT GGT TCT TTT GAT GT - #A GAT GAC GTC TCT AAT            96                                                                        Ala Cys Ser Gly Gly Gly Gly Ser Phe Asp Va - #l Asp Asp Val Ser Asn                         20     - #             25     - #             30                   - - CCC TCC TCT TCT AAA CCA CGT TAT CAA GAC GA - #T ACC TCG AGT CAA AGA           144                                                                        Pro Ser Ser Ser Lys Pro Arg Tyr Gln Asp As - #p Thr Ser Ser Gln Arg                     35         - #         40         - #         45                       - - ACA AAA TCT AAT TTG GAA AAG TTG TCC ATT CC - #T TCT TTA GGA GGA GGG           192                                                                        Thr Lys Ser Asn Leu Glu Lys Leu Ser Ile Pr - #o Ser Leu Gly Gly Gly                 50             - #     55             - #     60                           - - ATG AAA TTG GTG GCT CAG AAT CTG AGT GGT AA - #T AAA GAA CCT AGT TTC           240                                                                        Met Lys Leu Val Ala Gln Asn Leu Ser Gly As - #n Lys Glu Pro Ser Phe             65                 - # 70                 - # 75                 - # 80        - - TTA AAT GGA AAT GAC TAT ATG ATA TTT TCC TC - #A CGT TCT ACG ATT AAA           288                                                                        Leu Asn Gly Asn Asp Tyr Met Ile Phe Ser Se - #r Arg Ser Thr Ile Lys                             85 - #                 90 - #                 95               - - GAT GAT GTT GAA AAT AAC AAT ACA AAC GGG GG - #G GAC TAT ATT GGC TCA           336                                                                        Asp Asp Val Glu Asn Asn Asn Thr Asn Gly Gl - #y Asp Tyr Ile Gly Ser                        100      - #           105      - #           110                   - - ATA GAC GAG CCT AGT ACA ACA AAT CCA CTC GA - #A AAG CAT CAT GGA CAA           384                                                                        Ile Asp Glu Pro Ser Thr Thr Asn Pro Leu Gl - #u Lys His His Gly Gln                    115          - #       120          - #       125                       - - AGG TAT GTA TAT TCA GGG CTT TAT TAT ATT CA - #A TCG TGG AGT CTA AGA           432                                                                        Arg Tyr Val Tyr Ser Gly Leu Tyr Tyr Ile Gl - #n Ser Trp Ser Leu Arg                130              - #   135              - #   140                           - - GAT TTA CCA AAG AAG TTT TAT TCA GGT TAC TA - #T GGA TAT GCG TAT TAC           480                                                                        Asp Leu Pro Lys Lys Phe Tyr Ser Gly Tyr Ty - #r Gly Tyr Ala Tyr Tyr            145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - TTT GGC AAG GAA ACA GCC ACT ACA TTA CCT GT - #A AAT GGC GAA GCA         ACG      528                                                                     Phe Gly Lys Glu Thr Ala Thr Thr Leu Pro Va - #l Asn Gly Glu Ala Thr                           165  - #               170  - #               175               - - TAT AAA GGA ACT TGG GAT TTC ATC ACT GCA AC - #T AGA AAT GGC AAA AGT           576                                                                        Tyr Lys Gly Thr Trp Asp Phe Ile Thr Ala Th - #r Arg Asn Gly Lys Ser                        180      - #           185      - #           190                   - - TAT TCT TTG TTA AGT AAT AAC CGA CAA GCT TA - #T TCC AAA CGT AGT GCA           624                                                                        Tyr Ser Leu Leu Ser Asn Asn Arg Gln Ala Ty - #r Ser Lys Arg Ser Ala                    195          - #       200          - #       205                       - - ATT CCA GAA GAC ATT GAT TTA GAA AAT GAT CC - #A AAG AAT GGT GAG ACG           672                                                                        Ile Pro Glu Asp Ile Asp Leu Glu Asn Asp Pr - #o Lys Asn Gly Glu Thr                210              - #   215              - #   220                           - - AGA TTA ACT AGT GAA TTT ACT GTG AAT TTT GG - #T ACG AAA AAG CTC ACA           720                                                                        Arg Leu Thr Ser Glu Phe Thr Val Asn Phe Gl - #y Thr Lys Lys Leu Thr            225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - GGT GGA CTT TAT TAC CAT TTA CGT AAA ACA AA - #T GCT AAT GAA AAC         CAA      768                                                                     Gly Gly Leu Tyr Tyr His Leu Arg Lys Thr As - #n Ala Asn Glu Asn Gln                           245  - #               250  - #               255               - - AAT AGA AAA CAT AAA CTC TAC AAT CTA GAA GC - #T GAT GTG TAT AGC AAC           816                                                                        Asn Arg Lys His Lys Leu Tyr Asn Leu Glu Al - #a Asp Val Tyr Ser Asn                        260      - #           265      - #           270                   - - CGA TTC AGA GGT AAA GTA AAG CCA ACC AAA GA - #G TCT TCT GAA GAA CAT           864                                                                        Arg Phe Arg Gly Lys Val Lys Pro Thr Lys Gl - #u Ser Ser Glu Glu His                    275          - #       280          - #       285                       - - CCC TTT ACC AGC GAG GGA ACA TTA GAA GGT GG - #T TTT TAT GGG CCT AAT           912                                                                        Pro Phe Thr Ser Glu Gly Thr Leu Glu Gly Gl - #y Phe Tyr Gly Pro Asn                290              - #   295              - #   300                           - - GCT GAA GAA CTA GGG GGA AAA TTT TTA GCT AG - #C GAT AAA AAA GTT TTT           960                                                                        Ala Glu Glu Leu Gly Gly Lys Phe Leu Ala Se - #r Asp Lys Lys Val Phe            305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - GGG GTA TTT AGT GCC AAA GAA CAG CAA GAA AC - #G GAA GAA AAC AAA         AAA     1008                                                                     Gly Val Phe Ser Ala Lys Glu Gln Gln Glu Th - #r Glu Glu Asn Lys Lys                           325  - #               330  - #               335               - - TTA CTC AAA GAA ACC TTA ATT GAT GGC AAG CT - #A ACT ACT TTC TCT ACT          1056                                                                        Leu Leu Lys Glu Thr Leu Ile Asp Gly Lys Le - #u Thr Thr Phe Ser Thr                        340      - #           345      - #           350                   - - AAA AAA ACC AAT GCA ACA ACC GAT GCA ACA AC - #C AGT ACA ACA ACC AGT          1104                                                                        Lys Lys Thr Asn Ala Thr Thr Asp Ala Thr Th - #r Ser Thr Thr Thr Ser                    355          - #       360          - #       365                       - - ACA GCA ACC AAT GCA ACA GCC GAT GCA GAA AA - #C TTT ACG ACA AAA GAT          1152                                                                        Thr Ala Thr Asn Ala Thr Ala Asp Ala Glu As - #n Phe Thr Thr Lys Asp                370              - #   375              - #   380                           - - ATA TCA AGT TTT GGT GAA GCT GAT TAT CTT TT - #A ATT GAT AAT TAC CCT          1200                                                                        Ile Ser Ser Phe Gly Glu Ala Asp Tyr Leu Le - #u Ile Asp Asn Tyr Pro            385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - GTT CCT CTT TTA CCT GAA AAT ACT AAT GAT TT - #C ATA AGC AGT AAG         CAC     1248                                                                     Val Pro Leu Leu Pro Glu Asn Thr Asn Asp Ph - #e Ile Ser Ser Lys His                           405  - #               410  - #               415               - - CAT GAG GTA GGA GGT AAA CAC TAT AAA GTG GA - #A GCA TGT TGC AAG AAT          1296                                                                        His Glu Val Gly Gly Lys His Tyr Lys Val Gl - #u Ala Cys Cys Lys Asn                        420      - #           425      - #           430                   - - CTA AGC TAT GTG AAA TTT GGT ATA TAT TAT GA - #G GAT AAT GAG AAG AAC          1344                                                                        Leu Ser Tyr Val Lys Phe Gly Ile Tyr Tyr Gl - #u Asp Asn Glu Lys Asn                    435          - #       440          - #       445                       - - ACC AAA ATT GAA ACA GAA CAA TAC CAC CAA TT - #T TTG TTA GGT CTC CGT          1392                                                                        Thr Lys Ile Glu Thr Glu Gln Tyr His Gln Ph - #e Leu Leu Gly Leu Arg                450              - #   455              - #   460                           - - ACT CCC AGT TCT CAA ATT CCT GCA ACG GGA AA - #C GTG AAA TAT CGC GGT          1440                                                                        Thr Pro Ser Ser Gln Ile Pro Ala Thr Gly As - #n Val Lys Tyr Arg Gly            465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - AGT TGG TTT GGT TAT ATT GGT GAT GAC AAG AC - #A TCT TAC TCC ACT         ACT     1488                                                                     Ser Trp Phe Gly Tyr Ile Gly Asp Asp Lys Th - #r Ser Tyr Ser Thr Thr                           485  - #               490  - #               495               - - GGA GAT AAA AAT GCT CTC GCC GAG TTT GAT GT - #A AAT TTT ACC GAT AAA          1536                                                                        Gly Asp Lys Asn Ala Leu Ala Glu Phe Asp Va - #l Asn Phe Thr Asp Lys                        500      - #           505      - #           510                   - - AAG CTA ACA GGC GAA TTA AAA CGA GCC GAT AA - #T CAA AAT ACC GTA TTT          1584                                                                        Lys Leu Thr Gly Glu Leu Lys Arg Ala Asp As - #n Gln Asn Thr Val Phe                    515          - #       520          - #       525                       - - AGA ATT AAT GCA GAC TTT AAA AAT AAT GAT AA - #T GCC TTC AAA GGT ACA          1632                                                                        Arg Ile Asn Ala Asp Phe Lys Asn Asn Asp As - #n Ala Phe Lys Gly Thr                530              - #   535              - #   540                           - - GCA ACC GCA GAA AAT TTT GTA ATA GAT GGT AA - #C AAT AGT CAA ACT GGA          1680                                                                        Ala Thr Ala Glu Asn Phe Val Ile Asp Gly As - #n Asn Ser Gln Thr Gly            545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - AAT ACC CAA ATT AAT ATT AAA ACT GAA GTA AA - #T GGG GCA TTT TAT         GGT     1728                                                                     Asn Thr Gln Ile Asn Ile Lys Thr Glu Val As - #n Gly Ala Phe Tyr Gly                           565  - #               570  - #               575               - - CCG AAC GCT ACA GAA TTA GGC GGT TAT TTC AC - #T TAT AAC GGA AAA AAT          1776                                                                        Pro Asn Ala Thr Glu Leu Gly Gly Tyr Phe Th - #r Tyr Asn Gly Lys Asn                        580      - #           585      - #           590                   - - CCT ACA GAT AAA AAT TCT GAA AGT TCC TCA AC - #C GTA CCT TCA CCA CCC          1824                                                                        Pro Thr Asp Lys Asn Ser Glu Ser Ser Ser Th - #r Val Pro Ser Pro Pro                    595          - #       600          - #       605                       - - AAT TCA CCA AAT GCA AGA GCT GCA GTT GTC TT - #T GGT GCT AAA AAA CAA          1872                                                                        Asn Ser Pro Asn Ala Arg Ala Ala Val Val Ph - #e Gly Ala Lys Lys Gln                610              - #   615              - #   620                           - - GTA GAA AAA AAC AAC AAG TAAAAACAAC CAAGTAATGG AA - #TACTAAAA                 1920                                                                        Val Glu Lys Asn Asn Lys                                                        625                 6 - #30                                                     - - ATGACTAAAA AAGCTTCTAG AAGCCGAATT C        - #                  - #             1951                                                                       - -  - - (2) INFORMATION FOR SEQ ID NO: 113:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 630 amino - #acids                                                 (B) TYPE: amino acid                                                           (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #113:                          - - Met Lys Ser Val Pro Leu Ile Ser Gly Gly Le - #u Ser Leu Leu Leu Ser         1               5 - #                 10 - #                 15               - - Ala Cys Ser Gly Gly Gly Gly Ser Phe Asp Va - #l Asp Asp Val Ser Asn                    20     - #             25     - #             30                   - - Pro Ser Ser Ser Lys Pro Arg Tyr Gln Asp As - #p Thr Ser Ser Gln Arg                35         - #         40         - #         45                       - - Thr Lys Ser Asn Leu Glu Lys Leu Ser Ile Pr - #o Ser Leu Gly Gly Gly            50             - #     55             - #     60                           - - Met Lys Leu Val Ala Gln Asn Leu Ser Gly As - #n Lys Glu Pro Ser Phe        65                 - # 70                 - # 75                 - # 80        - - Leu Asn Gly Asn Asp Tyr Met Ile Phe Ser Se - #r Arg Ser Thr Ile Lys                        85 - #                 90 - #                 95               - - Asp Asp Val Glu Asn Asn Asn Thr Asn Gly Gl - #y Asp Tyr Ile Gly Ser                   100      - #           105      - #           110                   - - Ile Asp Glu Pro Ser Thr Thr Asn Pro Leu Gl - #u Lys His His Gly Gln               115          - #       120          - #       125                       - - Arg Tyr Val Tyr Ser Gly Leu Tyr Tyr Ile Gl - #n Ser Trp Ser Leu Arg           130              - #   135              - #   140                           - - Asp Leu Pro Lys Lys Phe Tyr Ser Gly Tyr Ty - #r Gly Tyr Ala Tyr Tyr       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Phe Gly Lys Glu Thr Ala Thr Thr Leu Pro Va - #l Asn Gly Glu Ala         Thr                                                                                              165  - #               170  - #               175              - - Tyr Lys Gly Thr Trp Asp Phe Ile Thr Ala Th - #r Arg Asn Gly Lys Ser                   180      - #           185      - #           190                   - - Tyr Ser Leu Leu Ser Asn Asn Arg Gln Ala Ty - #r Ser Lys Arg Ser Ala               195          - #       200          - #       205                       - - Ile Pro Glu Asp Ile Asp Leu Glu Asn Asp Pr - #o Lys Asn Gly Glu Thr           210              - #   215              - #   220                           - - Arg Leu Thr Ser Glu Phe Thr Val Asn Phe Gl - #y Thr Lys Lys Leu Thr       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Gly Gly Leu Tyr Tyr His Leu Arg Lys Thr As - #n Ala Asn Glu Asn         Gln                                                                                              245  - #               250  - #               255              - - Asn Arg Lys His Lys Leu Tyr Asn Leu Glu Al - #a Asp Val Tyr Ser Asn                   260      - #           265      - #           270                   - - Arg Phe Arg Gly Lys Val Lys Pro Thr Lys Gl - #u Ser Ser Glu Glu His               275          - #       280          - #       285                       - - Pro Phe Thr Ser Glu Gly Thr Leu Glu Gly Gl - #y Phe Tyr Gly Pro Asn           290              - #   295              - #   300                           - - Ala Glu Glu Leu Gly Gly Lys Phe Leu Ala Se - #r Asp Lys Lys Val Phe       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Gly Val Phe Ser Ala Lys Glu Gln Gln Glu Th - #r Glu Glu Asn Lys         Lys                                                                                              325  - #               330  - #               335              - - Leu Leu Lys Glu Thr Leu Ile Asp Gly Lys Le - #u Thr Thr Phe Ser Thr                   340      - #           345      - #           350                   - - Lys Lys Thr Asn Ala Thr Thr Asp Ala Thr Th - #r Ser Thr Thr Thr Ser               355          - #       360          - #       365                       - - Thr Ala Thr Asn Ala Thr Ala Asp Ala Glu As - #n Phe Thr Thr Lys Asp           370              - #   375              - #   380                           - - Ile Ser Ser Phe Gly Glu Ala Asp Tyr Leu Le - #u Ile Asp Asn Tyr Pro       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Val Pro Leu Leu Pro Glu Asn Thr Asn Asp Ph - #e Ile Ser Ser Lys         His                                                                                              405  - #               410  - #               415              - - His Glu Val Gly Gly Lys His Tyr Lys Val Gl - #u Ala Cys Cys Lys Asn                   420      - #           425      - #           430                   - - Leu Ser Tyr Val Lys Phe Gly Ile Tyr Tyr Gl - #u Asp Asn Glu Lys Asn               435          - #       440          - #       445                       - - Thr Lys Ile Glu Thr Glu Gln Tyr His Gln Ph - #e Leu Leu Gly Leu Arg           450              - #   455              - #   460                           - - Thr Pro Ser Ser Gln Ile Pro Ala Thr Gly As - #n Val Lys Tyr Arg Gly       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Ser Trp Phe Gly Tyr Ile Gly Asp Asp Lys Th - #r Ser Tyr Ser Thr         Thr                                                                                              485  - #               490  - #               495              - - Gly Asp Lys Asn Ala Leu Ala Glu Phe Asp Va - #l Asn Phe Thr Asp Lys                   500      - #           505      - #           510                   - - Lys Leu Thr Gly Glu Leu Lys Arg Ala Asp As - #n Gln Asn Thr Val Phe               515          - #       520          - #       525                       - - Arg Ile Asn Ala Asp Phe Lys Asn Asn Asp As - #n Ala Phe Lys Gly Thr           530              - #   535              - #   540                           - - Ala Thr Ala Glu Asn Phe Val Ile Asp Gly As - #n Asn Ser Gln Thr Gly       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Asn Thr Gln Ile Asn Ile Lys Thr Glu Val As - #n Gly Ala Phe Tyr         Gly                                                                                              565  - #               570  - #               575              - - Pro Asn Ala Thr Glu Leu Gly Gly Tyr Phe Th - #r Tyr Asn Gly Lys Asn                   580      - #           585      - #           590                   - - Pro Thr Asp Lys Asn Ser Glu Ser Ser Ser Th - #r Val Pro Ser Pro Pro               595          - #       600          - #       605                       - - Asn Ser Pro Asn Ala Arg Ala Ala Val Val Ph - #e Gly Ala Lys Lys Gln           610              - #   615              - #   620                           - - Val Glu Lys Asn Asn Lys                                                   625                 6 - #30                                                     - -  - - (2) INFORMATION FOR SEQ ID NO: 114:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 1955 base - #pairs                                                 (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (ix) FEATURE:                                                                   (A) NAME/KEY: CDS                                                              (B) LOCATION: 1..1893                                                 - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #114:                          - - ATG AAA TCT GTA CCT CTT ATC TCT GGT GGA CT - #T TCC TTT TTA CTA AGT            48                                                                        Met Lys Ser Val Pro Leu Ile Ser Gly Gly Le - #u Ser Phe Leu Leu Ser              1               5 - #                 10 - #                 15               - - GCT TGT AGC GGA GGG GGG TCT TTT GAT GTA GA - #T AAC GTC TCT AAT ACC            96                                                                        Ala Cys Ser Gly Gly Gly Ser Phe Asp Val As - #p Asn Val Ser Asn Thr                         20     - #             25     - #             30                   - - CCC TCT TCT AAA CCA CGT TAT CAA GAC GAT AC - #C TCG AAT CAA AGA ACA           144                                                                        Pro Ser Ser Lys Pro Arg Tyr Gln Asp Asp Th - #r Ser Asn Gln Arg Thr                     35         - #         40         - #         45                       - - AAA TCT AAA TTG GAA AAG TTG TCC ATT CCT TC - #T TTA GGA GGA GGG ATG           192                                                                        Lys Ser Lys Leu Glu Lys Leu Ser Ile Pro Se - #r Leu Gly Gly Gly Met                 50             - #     55             - #     60                           - - AAG TTA GTT GTG CAA AAT TTT GCT GGT GCT AA - #A GAA CCT AGT TTC TTA           240                                                                        Lys Leu Val Val Gln Asn Phe Ala Gly Ala Ly - #s Glu Pro Ser Phe Leu             65                 - # 70                 - # 75                 - # 80        - - AAT GAA AAT GAC TAT ATA TCA TAT TTT TCC TC - #A CTT TCT ATG ATT AAA           288                                                                        Asn Glu Asn Asp Tyr Ile Ser Tyr Phe Ser Se - #r Leu Ser Met Ile Lys                             85 - #                 90 - #                 95               - - GAT GAT GTT GAA AAT AAC AAT AAA AAT AAG GA - #T ACT CCA ATT GGC TCA           336                                                                        Asp Asp Val Glu Asn Asn Asn Lys Asn Lys As - #p Thr Pro Ile Gly Ser                        100      - #           105      - #           110                   - - ATA GAC GAG CCT AGA GCA CCA AAT TCA AAC GA - #A AAT CAT CAA AAT CAT           384                                                                        Ile Asp Glu Pro Arg Ala Pro Asn Ser Asn Gl - #u Asn His Gln Asn His                    115          - #       120          - #       125                       - - CAT GGA CAG CAA TAT GTA TAT TCG GGT CTT TA - #T TAT ATT CCA TCG TGG           432                                                                        His Gly Gln Gln Tyr Val Tyr Ser Gly Leu Ty - #r Tyr Ile Pro Ser Trp                130              - #   135              - #   140                           - - CGT CTA ATA AAT TTA CCA AAT AAG TTT TAT TC - #A GGT TAC TAT GGA TAT           480                                                                        Arg Leu Ile Asn Leu Pro Asn Lys Phe Tyr Se - #r Gly Tyr Tyr Gly Tyr            145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - GCG TAT TAC TTT GGC AAG CAA ACT GCC ACT AC - #A TTA CCT GTA AAT         GGC      528                                                                     Ala Tyr Tyr Phe Gly Lys Gln Thr Ala Thr Th - #r Leu Pro Val Asn Gly                           165  - #               170  - #               175               - - GAA GCA ACG TAT AAA GGA ACT TGG AGC TTC AT - #C ACC GCA ACT GAA AGA           576                                                                        Glu Ala Thr Tyr Lys Gly Thr Trp Ser Phe Il - #e Thr Ala Thr Glu Arg                        180      - #           185      - #           190                   - - GGC AAA AAT TAT TCT TTG TTC AAT AAT AGA GG - #T CAA GCT TAT TCT CGA           624                                                                        Gly Lys Asn Tyr Ser Leu Phe Asn Asn Arg Gl - #y Gln Ala Tyr Ser Arg                    195          - #       200          - #       205                       - - CGT AGT GCT ACT CCA GGA GAT ATT GAT TTA GA - #A AAC GGT GAC GCA GGC           672                                                                        Arg Ser Ala Thr Pro Gly Asp Ile Asp Leu Gl - #u Asn Gly Asp Ala Gly                210              - #   215              - #   220                           - - TTA ACA AGT GAA TTT ACT GTC AAT TTT GGT AC - #A AAA AAG CTC ACT GGA           720                                                                        Leu Thr Ser Glu Phe Thr Val Asn Phe Gly Th - #r Lys Lys Leu Thr Gly            225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - GAA CCT TAT TAT AAT GAA AGG GAA ACA AAT CT - #T AAT CAA TCA AAA         GAT      768                                                                     Glu Pro Tyr Tyr Asn Glu Arg Glu Thr Asn Le - #u Asn Gln Ser Lys Asp                           245  - #               250  - #               255               - - AGA AAA CAT AAA CTC TAC GAT CTA GAA GCT GA - #T GTG TAT AGC AAC CGA           816                                                                        Arg Lys His Lys Leu Tyr Asp Leu Glu Ala As - #p Val Tyr Ser Asn Arg                        260      - #           265      - #           270                   - - TTC AGA GGT ACA GTA AAG CCA ACC AAA AAA GA - #G TCT TCT GAA GAA CAT           864                                                                        Phe Arg Gly Thr Val Lys Pro Thr Lys Lys Gl - #u Ser Ser Glu Glu His                    275          - #       280          - #       285                       - - CCC TTT ACC AGC GAG GGA ACA TTA GAA GGT GG - #T TTT TAT GGG CCT AAT           912                                                                        Pro Phe Thr Ser Glu Gly Thr Leu Glu Gly Gl - #y Phe Tyr Gly Pro Asn                290              - #   295              - #   300                           - - GCT GAA GAA CTA GGG GGA AAA TTT TTA GCT AG - #C GAT AAA AAA GTT TTT           960                                                                        Ala Glu Glu Leu Gly Gly Lys Phe Leu Ala Se - #r Asp Lys Lys Val Phe            305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - GGG GTA TTT AGT GCC AAA GAA ACG GAA GAA AA - #A CCA AAA TTA CCC         AAA     1008                                                                     Gly Val Phe Ser Ala Lys Glu Thr Glu Glu Ly - #s Pro Lys Leu Pro Lys                           325  - #               330  - #               335               - - GAA ACC TTA ATT GAT GGC AAG CTA ACT ACT TT - #C TCT AAA ACA ACC GAT          1056                                                                        Glu Thr Leu Ile Asp Gly Lys Leu Thr Thr Ph - #e Ser Lys Thr Thr Asp                        340      - #           345      - #           350                   - - ACA ACA ACC AAT AAA ACA ACC AGT GCA AAA AC - #C AAT ACA GAA AAC TTT          1104                                                                        Thr Thr Thr Asn Lys Thr Thr Ser Ala Lys Th - #r Asn Thr Glu Asn Phe                    355          - #       360          - #       365                       - - ACG ACA AAA GAT ATA CCA AGT TTT GGT GAA GC - #T GAT TAT CTT TTA ATT          1152                                                                        Thr Thr Lys Asp Ile Pro Ser Phe Gly Glu Al - #a Asp Tyr Leu Leu Ile                370              - #   375              - #   380                           - - GAT AAT TAC CCT ATT CCG CTT TTA CCT GAG AG - #T GGT GAT TTC ATA AGT          1200                                                                        Asp Asn Tyr Pro Ile Pro Leu Leu Pro Glu Se - #r Gly Asp Phe Ile Ser            385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - AGT AAG CAC CAT GAG GTA GGA GGT AAA CGC TA - #T AAA GTG GAA GCA         TGT     1248                                                                     Ser Lys His His Glu Val Gly Gly Lys Arg Ty - #r Lys Val Glu Ala Cys                           405  - #               410  - #               415               - - TGC AAG AAT CTA TGC TAT GTG AAA TTT GGT AT - #G TAT TAT GAG GAT AAA          1296                                                                        Cys Lys Asn Leu Cys Tyr Val Lys Phe Gly Me - #t Tyr Tyr Glu Asp Lys                        420      - #           425      - #           430                   - - GAG AAC AAC AAA AAT GAA ACA GAC AAA GAA AA - #A GAA AAA CAA ACG ACA          1344                                                                        Glu Asn Asn Lys Asn Glu Thr Asp Lys Glu Ly - #s Glu Lys Gln Thr Thr                    435          - #       440          - #       445                       - - ACA TCT ATC AAG ACT TAT TAT CAA TTC TTA TT - #A GGT CTC CGG ACT CCC          1392                                                                        Thr Ser Ile Lys Thr Tyr Tyr Gln Phe Leu Le - #u Gly Leu Arg Thr Pro                450              - #   455              - #   460                           - - AGT TCT GAA ATT CCT AAA ATG GGA AAC GTG AC - #A TAT CGC GGT AGT TGG          1440                                                                        Ser Ser Glu Ile Pro Lys Met Gly Asn Val Th - #r Tyr Arg Gly Ser Trp            465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - TTT GGT TAT ATT GGT GAT GAC AAG ACA TCT TA - #C TCC GCT ACA GGA         GAT     1488                                                                     Phe Gly Tyr Ile Gly Asp Asp Lys Thr Ser Ty - #r Ser Ala Thr Gly Asp                           485  - #               490  - #               495               - - AAA CGA CAA GAT AAA AAT GCT CCC GCC GAG TT - #T AAT GCT GAT TTT AAC          1536                                                                        Lys Arg Gln Asp Lys Asn Ala Pro Ala Glu Ph - #e Asn Ala Asp Phe Asn                        500      - #           505      - #           510                   - - AAT AAA AAG CTA ACA GGC ACA TCA AAA CGA CA - #C GAT AAT CAA AAT CCC          1584                                                                        Asn Lys Lys Leu Thr Gly Thr Ser Lys Arg Hi - #s Asp Asn Gln Asn Pro                    515          - #       520          - #       525                       - - GTG TTT AAC ATT AAG GCA ACC TTT CAA AAT GG - #T CGG AAT GAC TTT GAA          1632                                                                        Val Phe Asn Ile Lys Ala Thr Phe Gln Asn Gl - #y Arg Asn Asp Phe Glu                530              - #   535              - #   540                           - - GGT ACA GCA ACC GCA GAA AAT TTT GTA ATA GA - #T GGT AAA GAT AGT CAA          1680                                                                        Gly Thr Ala Thr Ala Glu Asn Phe Val Ile As - #p Gly Lys Asp Ser Gln            545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - GGA AAT ACC CCA ATT AAT ATT ACA ACT AAA GT - #A AAC GGG GCA TTT         TAT     1728                                                                     Gly Asn Thr Pro Ile Asn Ile Thr Thr Lys Va - #l Asn Gly Ala Phe Tyr                           565  - #               570  - #               575               - - GGA CCT GAT GCT TCT GAA TTA GGC GGT TAT TT - #C ACC TAT AAC GGA AAA          1776                                                                        Gly Pro Asp Ala Ser Glu Leu Gly Gly Tyr Ph - #e Thr Tyr Asn Gly Lys                        580      - #           585      - #           590                   - - GAC ACT ATA ACT AAA AAT ACT GAA AGT TCC TC - #A ACC GTA CCT TCA CCA          1824                                                                        Asp Thr Ile Thr Lys Asn Thr Glu Ser Ser Se - #r Thr Val Pro Ser Pro                    595          - #       600          - #       605                       - - CCC AAT TCA CCA AAT GCA AGA GCT GCA GTT GT - #G TTT GGA GCT AAA AAA          1872                                                                        Pro Asn Ser Pro Asn Ala Arg Ala Ala Val Va - #l Phe Gly Ala Lys Lys                610              - #   615              - #   620                           - - CAA GTA GAA ACA ACC AAC AAG TAGAAAAAAA CAAATAATG - #G AATACTAAAA             1923                                                                        Gln Val Glu Thr Thr Asn Lys                                                    625                 6 - #30                                                     - - ATGACTAAAA AAGCTTCTAG AAAGCCGAAT TC       - #                  - #             1955                                                                       - -  - - (2) INFORMATION FOR SEQ ID NO: 115:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 631 amino - #acids                                                 (B) TYPE: amino acid                                                           (D) TOPOLOGY: linear                                                  - -     (ii) MOLECULE TYPE: protein                                            - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #115:                          - - Met Lys Ser Val Pro Leu Ile Ser Gly Gly Le - #u Ser Phe Leu Leu Ser         1               5 - #                 10 - #                 15               - - Ala Cys Ser Gly Gly Gly Ser Phe Asp Val As - #p Asn Val Ser Asn Thr                    20     - #             25     - #             30                   - - Pro Ser Ser Lys Pro Arg Tyr Gln Asp Asp Th - #r Ser Asn Gln Arg Thr                35         - #         40         - #         45                       - - Lys Ser Lys Leu Glu Lys Leu Ser Ile Pro Se - #r Leu Gly Gly Gly Met            50             - #     55             - #     60                           - - Lys Leu Val Val Gln Asn Phe Ala Gly Ala Ly - #s Glu Pro Ser Phe Leu        65                 - # 70                 - # 75                 - # 80        - - Asn Glu Asn Asp Tyr Ile Ser Tyr Phe Ser Se - #r Leu Ser Met Ile Lys                        85 - #                 90 - #                 95               - - Asp Asp Val Glu Asn Asn Asn Lys Asn Lys As - #p Thr Pro Ile Gly Ser                   100      - #           105      - #           110                   - - Ile Asp Glu Pro Arg Ala Pro Asn Ser Asn Gl - #u Asn His Gln Asn His               115          - #       120          - #       125                       - - His Gly Gln Gln Tyr Val Tyr Ser Gly Leu Ty - #r Tyr Ile Pro Ser Trp           130              - #   135              - #   140                           - - Arg Leu Ile Asn Leu Pro Asn Lys Phe Tyr Se - #r Gly Tyr Tyr Gly Tyr       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Ala Tyr Tyr Phe Gly Lys Gln Thr Ala Thr Th - #r Leu Pro Val Asn         Gly                                                                                              165  - #               170  - #               175              - - Glu Ala Thr Tyr Lys Gly Thr Trp Ser Phe Il - #e Thr Ala Thr Glu Arg                   180      - #           185      - #           190                   - - Gly Lys Asn Tyr Ser Leu Phe Asn Asn Arg Gl - #y Gln Ala Tyr Ser Arg               195          - #       200          - #       205                       - - Arg Ser Ala Thr Pro Gly Asp Ile Asp Leu Gl - #u Asn Gly Asp Ala Gly           210              - #   215              - #   220                           - - Leu Thr Ser Glu Phe Thr Val Asn Phe Gly Th - #r Lys Lys Leu Thr Gly       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Glu Pro Tyr Tyr Asn Glu Arg Glu Thr Asn Le - #u Asn Gln Ser Lys         Asp                                                                                              245  - #               250  - #               255              - - Arg Lys His Lys Leu Tyr Asp Leu Glu Ala As - #p Val Tyr Ser Asn Arg                   260      - #           265      - #           270                   - - Phe Arg Gly Thr Val Lys Pro Thr Lys Lys Gl - #u Ser Ser Glu Glu His               275          - #       280          - #       285                       - - Pro Phe Thr Ser Glu Gly Thr Leu Glu Gly Gl - #y Phe Tyr Gly Pro Asn           290              - #   295              - #   300                           - - Ala Glu Glu Leu Gly Gly Lys Phe Leu Ala Se - #r Asp Lys Lys Val Phe       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Gly Val Phe Ser Ala Lys Glu Thr Glu Glu Ly - #s Pro Lys Leu Pro         Lys                                                                                              325  - #               330  - #               335              - - Glu Thr Leu Ile Asp Gly Lys Leu Thr Thr Ph - #e Ser Lys Thr Thr Asp                   340      - #           345      - #           350                   - - Thr Thr Thr Asn Lys Thr Thr Ser Ala Lys Th - #r Asn Thr Glu Asn Phe               355          - #       360          - #       365                       - - Thr Thr Lys Asp Ile Pro Ser Phe Gly Glu Al - #a Asp Tyr Leu Leu Ile           370              - #   375              - #   380                           - - Asp Asn Tyr Pro Ile Pro Leu Leu Pro Glu Se - #r Gly Asp Phe Ile Ser       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Ser Lys His His Glu Val Gly Gly Lys Arg Ty - #r Lys Val Glu Ala         Cys                                                                                              405  - #               410  - #               415              - - Cys Lys Asn Leu Cys Tyr Val Lys Phe Gly Me - #t Tyr Tyr Glu Asp Lys                   420      - #           425      - #           430                   - - Glu Asn Asn Lys Asn Glu Thr Asp Lys Glu Ly - #s Glu Lys Gln Thr Thr               435          - #       440          - #       445                       - - Thr Ser Ile Lys Thr Tyr Tyr Gln Phe Leu Le - #u Gly Leu Arg Thr Pro           450              - #   455              - #   460                           - - Ser Ser Glu Ile Pro Lys Met Gly Asn Val Th - #r Tyr Arg Gly Ser Trp       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Phe Gly Tyr Ile Gly Asp Asp Lys Thr Ser Ty - #r Ser Ala Thr Gly         Asp                                                                                              485  - #               490  - #               495              - - Lys Arg Gln Asp Lys Asn Ala Pro Ala Glu Ph - #e Asn Ala Asp Phe Asn                   500      - #           505      - #           510                   - - Asn Lys Lys Leu Thr Gly Thr Ser Lys Arg Hi - #s Asp Asn Gln Asn Pro               515          - #       520          - #       525                       - - Val Phe Asn Ile Lys Ala Thr Phe Gln Asn Gl - #y Arg Asn Asp Phe Glu           530              - #   535              - #   540                           - - Gly Thr Ala Thr Ala Glu Asn Phe Val Ile As - #p Gly Lys Asp Ser Gln       545                 5 - #50                 5 - #55                 5 -       #60                                                                               - - Gly Asn Thr Pro Ile Asn Ile Thr Thr Lys Va - #l Asn Gly Ala Phe         Tyr                                                                                              565  - #               570  - #               575              - - Gly Pro Asp Ala Ser Glu Leu Gly Gly Tyr Ph - #e Thr Tyr Asn Gly Lys                   580      - #           585      - #           590                   - - Asp Thr Ile Thr Lys Asn Thr Glu Ser Ser Se - #r Thr Val Pro Ser Pro               595          - #       600          - #       605                       - - Pro Asn Ser Pro Asn Ala Arg Ala Ala Val Va - #l Phe Gly Ala Lys Lys           610              - #   615              - #   620                           - - Gln Val Glu Thr Thr Asn Lys                                               625                 6 - #30                                                     - -  - - (2) INFORMATION FOR SEQ ID NO: 116:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 100 base - #pairs                                                  (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #116:                          - - TCTAACTTGA CATTATTACA AAAAAAGATC AATAATGCGA ATTATTATCA AT -              #TTTGTATG     60                                                                  - - AGTATATAAT TCTATGAAAT CTGTACCTCT TATCTCTGGT     - #                       - #   100                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO: 117:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 100 base - #pairs                                                  (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #117:                          - - TCTAACTTGA CATTATTACA AAAAAAGATC AATAATGCGA ATTATTATCA AT -              #TTTGTATG     60                                                                  - - AGTATATAAT TCTATGAAAT CTGTACCTCT TATCTCTGGT     - #                       - #   100                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO: 118:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 99 base - #pairs                                                   (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #118:                          - - TCTAAGTTGA CATTATTACA AAAAAAGAAC AATAATGCGA ATTATTATCA AT -              #TTTGTATA     60                                                                  - - AGTATTAATT CTATGAAATC TGTACCTCTT ATCTCTGGT      - #                       - #    99                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO: 119:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 100 base - #pairs                                                  (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #119:                          - - TCTAAGTTGA CATTATTACA AAAAAAGAAC AATAATGCGA ATTATTATCA AT -              #TTTGTATA     60                                                                  - - AGAATATAAT TCTATGAAAT CTGTACCTCT TATCTCTGGT     - #                       - #   100                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO: 120:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 35 base - #pairs                                                   (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #120:                          - - GGATCCATAT GAAATCTGTA CCTCTTATCT CTGGT       - #                  -      #       35                                                                       - -  - - (2) INFORMATION FOR SEQ ID NO: 121:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 61 base - #pairs                                                   (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #121:                          - - GTAGAAACAA CCAAATAATG GAATACTAAA AATGACTAAA AAACCCTATT TT -              #CGCCTAAG     60                                                                  - - T                  - #                  - #                  - #                    61                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO: 122:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 61 base - #pairs                                                   (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #122:                          - - GTAGAAACAA CCAAATAATG GAATACTAAA AATGACTAAA AAACCCTATT TT -              #CGCCTAAG     60                                                                  - - T                  - #                  - #                  - #                    61                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO: 123:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 61 base - #pairs                                                   (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #123:                          - - GTAGAAACAA CCAAGTAATG GAATACTAAA AATGACTAAA AAACCCTATT TT -              #CGCCTAAG     60                                                                  - - T                  - #                  - #                  - #                    61                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO: 124:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 78 base - #pairs                                                   (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #124:                          - - GTAGAAACAA CCAACAAGTA AAAACAACCA AGTAATGGAA TACTAAAAAT GA -              #CTAAAAAA     60                                                                  - - CCCTATTTTC GCCTAAGT             - #                  - #                       - #  78                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO: 125:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 43 base - #pairs                                                   (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #125:                          - - GTAGAAACAA CCAAATAATG GAATACTAAA AATGACTAAA AAA    - #                       - # 43                                                                       - -  - - (2) INFORMATION FOR SEQ ID NO: 126:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 60 base - #pairs                                                   (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #126:                          - - GTAGAAACAA CCAACAAGTA AAAACAACCA AGTAATGGAA TACTAAAAAT GA -              #CTAAAAAA     60                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO: 127:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 60 base - #pairs                                                   (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #127:                          - - GTAGAAAAAA ACAACTAGTA AAAACAACCA AGTAATGGAA TACTAAAAAT GA -             #CTAAAAAA     60                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO: 128:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 60 base - #pairs                                                   (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #128:                          - - GTAGAAACAA CCAACAAGTA GAAAAAAACA AATAATGGAA TACTAAAAAT GA -             #CTAAAAAA     60                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO: 129:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 35 base - #pairs                                                   (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #129:                          - - TCTAGAAGCT TTTTTAGTCA TTTTTAGTAT TCCAT       - #                        - #       35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO: 130:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 58 base - #pairs                                                   (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #130:                          - - TATGTGTTCT GGTGGTGGTT CTTTCGACGT TGACAACGTT TCTAACACTC CC -             #TCTTCT       58                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO: 131:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 59 base - #pairs                                                   (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #131:                          - - ACACAAGACC ACCACCAAGA AAGCTGCAAC TGTTGCAAAG ATTGTGAGGG AG -             #AAGATTT      59                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO: 132:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 9 amino - #acids                                                   (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #132:                          - - Asn Pro Ala Ser Thr Thr Asn Lys Asp                                       1               5                                                               - -  - - (2) INFORMATION FOR SEQ ID NO: 133:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 17 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #133:                          - - Asn Pro Ala Ser Thr Thr Ser Leu Glu Gly Gl - #y Phe Tyr Gly Pro         Lys                                                                              1               5   - #                10  - #                15               - - Asp                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO: 134:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 16 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #134:                          - - Asn Pro Ala Ser Thr Thr Ser Leu Glu Gly Gl - #y Phe Tyr Gly Lys Asp       1               5   - #                10  - #                15                - -  - - (2) INFORMATION FOR SEQ ID NO: 135:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 16 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #135:                          - - Asn Pro Ala Ser Thr Thr Leu Glu Gly Gly Ph - #e Tyr Gly Pro Lys Asp       1               5   - #                10  - #                15                - -  - - (2) INFORMATION FOR SEQ ID NO: 136:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 15 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #136:                          - - Asn Pro Ala Ser Thr Thr Leu Glu Gly Gly Ph - #e Tyr Gly Lys Asp           1               5   - #                10  - #                15                - -  - - (2) INFORMATION FOR SEQ ID NO: 137:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 35 base - #pairs                                                   (B) TYPE: nucleic acid                                                         (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #137:                          - - TCTAGAAGCT TTTTTAGTCA TTTTTAGTAT TCCAT       - #                  -      #       35                                                                       - -  - - (2) INFORMATION FOR SEQ ID NO: 138:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 4 amino - #acids                                                   (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #138:                          - - Met Thr Lys Lys                                                            1                                                                              - -  - - (2) INFORMATION FOR SEQ ID NO: 139:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 5 amino - #acids                                                   (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #139:                          - - Glu Gln Val Leu Asn                                                       1               5                                                               - -  - - (2) INFORMATION FOR SEQ ID NO: 140:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 9 amino - #acids                                                   (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #140:                          - - Asp Ile Arg Asp Leu Thr Arg Tyr Asp                                       1               5                                                               - -  - - (2) INFORMATION FOR SEQ ID NO: 141:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 18 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #141:                          - - Gly Ala Ile Asn Glu Ile Glu Tyr Glu Asn Va - #l Lys Ala Val Glu Ile       1               5   - #                10  - #                15                - - Ser Lys                                                                    - -  - - (2) INFORMATION FOR SEQ ID NO: 142:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 5 amino - #acids                                                   (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #142:                          - - Val Tyr Asn Leu Phe                                                       1               5                                                               - -  - - (2) INFORMATION FOR SEQ ID NO: 143:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 9 amino - #acids                                                   (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #143:                          - - Leu Asn Tyr Arg Tyr Val Thr Trp Glu                                       1               5                                                               - -  - - (2) INFORMATION FOR SEQ ID NO: 144:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 9 amino - #acids                                                   (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #144:                          - - Cys Ser Gly Gly Gly Gly Ser Phe Asp                                       1               5                                                               - -  - - (2) INFORMATION FOR SEQ ID NO: 145:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 9 amino - #acids                                                   (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #145:                          - - Cys Leu Gly Gly Gly Gly Ser Phe Asp                                       1               5                                                               - -  - - (2) INFORMATION FOR SEQ ID NO: 146:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 8 amino - #acids                                                   (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #146:                          - - Leu Ser Gly Gly Phe Phe Gly Pro                                           1               5                                                               - -  - - (2) INFORMATION FOR SEQ ID NO: 147:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 10 amino - #acids                                                  (B) TYPE: amino acid                                                           (C) STRANDEDNESS: single                                                       (D) TOPOLOGY: linear                                                  - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #147:                          - - Met Lys Ser Val Pro Leu Ile Ser Gly Ser                                   1               5   - #                10                                     __________________________________________________________________________ 

What is claimed is:
 1. An isolated and purified antibody or a monospecific antiserum, wherein the antibody or antiserum is specific for a single transferrin receptor protein of a strain of Haemophilus influenzae or an immunogenic fragment thereof.
 2. The antibody or antiserum of claim 1, wherein the transferrin receptor protein of a strain of Haemophilus influenzae is Tbp1 or Tbp2.
 3. The antibody or antiserum of claim 1, wherein the transferrin receptor protein of a strain of Haemophilus influenzae comprises the sequence of any one of SEQ ID NO: 5-12, 106, 107, 109, 111, 113, and
 115. 4. The antibody or antiserum of claim 1, wherein the transferrin receptor protein of a strain of Haemophilus influenzae has been made by recombinant expression of DNA comprising the sequence of any one of SEQ ID NO: 1-4, 105, 108, 110, 112, and
 114. 5. The antibody or antiserum of claim 1, wherein the immunogenic fragment of a transferrin receptor protein of a strain of Haemophilus influenzae comprises the sequence of SEQ ID NO:74.
 6. The antibody or antiserum of claim 1, wherein the strain of Haemophilus influenzae is a strain of Haemophilus influenzae type b. 